ID SCN5A_HUMAN Reviewed; 2016 AA. AC Q14524; A5H1P8; A6N922; A6N923; B2RTU0; E7ET19; E9PEF3; E9PEK2; E9PFW7; AC Q59H93; Q75RX9; Q75RY0; Q86UR3; Q8IZC9; Q96J69; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 237. DE RecName: Full=Sodium channel protein type 5 subunit alpha; DE AltName: Full=Sodium channel protein cardiac muscle subunit alpha; DE AltName: Full=Sodium channel protein type V subunit alpha; DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.5; DE AltName: Full=hH1 {ECO:0000303|PubMed:1309946}; GN Name=SCN5A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND RP VARIANTS ARG-552 AND GLN-1027. RC TISSUE=Heart; RX PubMed=1309946; DOI=10.1073/pnas.89.2.554; RA Gellens M.E., George A.L. Jr., Chen L.Q., Chahine M., Horn R., Barchi R.L., RA Kallen R.G.; RT "Primary structure and functional expression of the human cardiac RT tetrodotoxin-insensitive voltage-dependent sodium channel."; RL Proc. Natl. Acad. Sci. U.S.A. 89:554-558(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND VARIANT RP ARG-552. RC TISSUE=Jejunal smooth muscle; RX PubMed=12358675; DOI=10.1046/j.1365-2982.2002.00348.x; RA Ou Y., Gibbons S.J., Miller S.M., Strege P.R., Rich A., Distad M.A., RA Ackerman M.J., Rae J.L., Szurszewski J.H., Farrugia G.; RT "SCN5A is expressed in human jejunal circular smooth muscle cells."; RL Neurogastroenterol. Motil. 14:477-486(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ARG-558 AND TYR-1103. RX PubMed=14500339; DOI=10.1161/01.res.0000096652.14509.96; RA Makielski J.C., Ye B., Valdivia C.R., Pagel M.D., Pu J., Tester D.J., RA Ackerman M.J.; RT "A ubiquitous splice variant and a common polymorphism affect heterologous RT expression of recombinant human SCN5A heart sodium channels."; RL Circ. Res. 93:821-828(2003). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-558, AND RP CHARACTERIZATION OF VARIANT LQT3 LEU-1766. RX PubMed=12454206; DOI=10.1152/physiolgenomics.00117.2002; RA Ye B., Valdivia C.R., Ackerman M.J., Makielski J.C.; RT "A common human SCN5A polymorphism modifies expression of an arrhythmia RT causing mutation."; RL Physiol. Genomics 12:187-193(2003). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), AND VARIANT THR-1498. RX PubMed=16115203; DOI=10.1111/j.1460-9568.2005.04280.x; RA Ou S.-W., Kameyama A., Hao L.-Y., Horiuchi M., Minobe E., Wang W.-Y., RA Makita N., Kameyama M.; RT "Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are RT encoded by new variants of Nav1.5/SCN5A."; RL Eur. J. Neurosci. 22:793-801(2005). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6), AND VARIANTS LEU-336 AND RP GLN-1027. RA Wang J., Ou S.-W., Wang Y.-J., Zong Z.-H.; RT "Cloning, distribution and analysis of the new exon encoding Nav1.5 channel RT in brain tissues."; RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 34:255-259(2007). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ARG-558. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 422-2016 (ISOFORMS 3/6). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP INTERACTION WITH NEDD4L, UBIQUITINATION, AND MUTAGENESIS OF TYR-1977 AND RP VAL-1980. RX PubMed=15217910; DOI=10.1161/01.res.0000136816.05109.89; RA van Bemmelen M.X., Rougier J.-S., Gavillet B., Apotheloz F., Daidie D., RA Tateyama M., Rivolta I., Thomas M.A., Kass R.S., Staub O., Abriel H.; RT "Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 RT mediated ubiquitination."; RL Circ. Res. 95:284-291(2004). RN [12] RP INTERACTION WITH NEDD4; NEDD4L AND WWP2, UBIQUITINATION, AND MUTAGENESIS OF RP PRO-1974; PRO-1975; SER-1976; TYR-1977; ASP-1978; SER-1979 AND VAL-1980. RX PubMed=15548568; DOI=10.1152/ajpcell.00460.2004; RA Rougier J.-S., van Bemmelen M.X., Bruce M.C., Jespersen T., Gavillet B., RA Apotheloz F., Cordonier S., Staub O., Rotin D., Abriel H.; RT "Molecular determinants of voltage-gated sodium channel regulation by the RT Nedd4/Nedd4-like proteins."; RL Am. J. Physiol. 288:C692-C701(2005). RN [13] RP MUTAGENESIS OF GLN-1476. RX PubMed=16054936; DOI=10.1016/s0140-6736(05)66786-4; RA Dichgans M., Freilinger T., Eckstein G., Babini E., Lorenz-Depiereux B., RA Biskup S., Ferrari M.D., Herzog J., van den Maagdenberg A.M.J.M., Pusch M., RA Strom T.M.; RT "Mutation in the neuronal voltage-gated sodium channel SCN1A in familial RT hemiplegic migraine."; RL Lancet 366:371-377(2005). RN [14] RP INTERACTION WITH GPD1L, AND PHOSPHORYLATION AT SER-1503 BY PKC. RX PubMed=19666841; DOI=10.1152/ajpheart.00513.2009; RA Valdivia C.R., Ueda K., Ackerman M.J., Makielski J.C.; RT "GPD1L links redox state to cardiac excitability by PKC-dependent RT phosphorylation of the sodium channel SCN5A."; RL Am. J. Physiol. 297:H1446-H1452(2009). RN [15] RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY (ISOFORM 4). RX PubMed=19376164; DOI=10.1016/j.neures.2009.04.003; RA Wang J., Ou S.-W., Wang Y.-J., Kameyama M., Kameyama A., Zong Z.-H.; RT "Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain."; RL Neurosci. Res. 64:339-347(2009). RN [16] RP REVIEW ON VARIANTS. RX PubMed=19027780; DOI=10.1016/j.pbiomolbio.2008.10.005; RA Zimmer T., Surber R.; RT "SCN5A channelopathies - An update on mutations and mechanisms."; RL Prog. Biophys. Mol. Biol. 98:120-136(2008). RN [17] RP ALTERNATIVE SPLICING. RX PubMed=20398673; DOI=10.1016/j.yjmcc.2010.04.004; RA Schroeter A., Walzik S., Blechschmidt S., Haufe V., Benndorf K., Zimmer T.; RT "Structure and function of splice variants of the cardiac voltage-gated RT sodium channel Na(v)1.5."; RL J. Mol. Cell. Cardiol. 49:16-24(2010). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21447824; DOI=10.1161/circgenetics.110.959130; RA Kattygnarath D., Maugenre S., Neyroud N., Balse E., Ichai C., Denjoy I., RA Dilanian G., Martins R.P., Fressart V., Berthet M., Schott J.J., RA Leenhardt A., Probst V., Le Marec H., Hainque B., Coulombe A., Hatem S.N., RA Guicheney P.; RT "MOG1: a new susceptibility gene for Brugada syndrome."; RL Circ. Cardiovasc. Genet. 4:261-268(2011). RN [19] RP INTERACTION WITH FGF13. RX PubMed=21817159; DOI=10.1161/circresaha.111.247957; RA Wang C., Hennessey J.A., Kirkton R.D., Wang C., Graham V., Puranam R.S., RA Rosenberg P.B., Bursac N., Pitt G.S.; RT "Fibroblast growth factor homologous factor 13 regulates Na+ channels and RT conduction velocity in murine hearts."; RL Circ. Res. 109:775-782(2011). RN [20] RP METHYLATION AT ARG-513; ARG-526 AND ARG-680. RX PubMed=21726068; DOI=10.1021/pr200339n; RA Beltran-Alvarez P., Pagans S., Brugada R.; RT "The cardiac sodium channel is post-translationally modified by arginine RT methylation."; RL J. Proteome Res. 10:3712-3719(2011). RN [21] RP PHOSPHORYLATION AT SER-36; THR-38; SER-457; SER-460; SER-483; SER-484; RP SER-497; SER-510; SER-571; SER-664 AND SER-667. RX PubMed=23092124; DOI=10.1021/pr300702c; RA Marionneau C., Lichti C.F., Lindenbaum P., Charpentier F., Nerbonne J.M., RA Townsend R.R., Merot J.; RT "Mass spectrometry-based identification of native cardiac Nav1.5 channel RT alpha subunit phosphorylation sites."; RL J. Proteome Res. 11:5994-6007(2012). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ATRST1 RP ASN-1275; VARIANT ASN-1275 BRGDA1; VARIANT ASN-1275 CMD1E; VARIANT PFHB1A RP ASN-1275 AND VARIANT BRGDA1 ARG-1743. RX PubMed=23420830; DOI=10.1161/circep.111.000206; RA Chakrabarti S., Wu X., Yang Z., Wu L., Yong S.L., Zhang C., Hu K., RA Wang Q.K., Chen Q.; RT "MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada RT syndrome and sick sinus syndrome."; RL Circ. Arrhythm. Electrophysiol. 6:392-401(2013). RN [23] RP MUTAGENESIS OF ASP-1610. RX PubMed=24898004; DOI=10.1124/mol.114.092338; RA Xiao Y., Blumenthal K., Cummins T.R.; RT "Gating-pore currents demonstrate selective and specific modulation of RT individual sodium channel voltage-sensors by biological toxins."; RL Mol. Pharmacol. 86:159-167(2014). RN [24] RP MUTAGENESIS OF ASP-1610 AND LYS-1614, AND SUBUNIT. RX PubMed=26721415; DOI=10.1016/j.toxicon.2015.12.009; RA Tao H., Chen X., Lu M., Wu Y., Deng M., Zeng X., Liu Z., Liang S.; RT "Molecular determinant for the tarantula toxin Jingzhaotoxin-I slowing the RT fast inactivation of voltage-gated sodium channels."; RL Toxicon 111:13-21(2016). RN [25] RP SUBUNIT. RX PubMed=37117223; DOI=10.1038/s41467-023-37963-2; RA Jami S., Deuis J.R., Klasfauseweh T., Cheng X., Kurdyukov S., Chung F., RA Okorokov A.L., Li S., Zhang J., Cristofori-Armstrong B., Israel M.R., RA Ju R.J., Robinson S.D., Zhao P., Ragnarsson L., Andersson A., Tran P., RA Schendel V., McMahon K.L., Tran H.N.T., Chin Y.K., Zhu Y., Liu J., RA Crawford T., Purushothamvasan S., Habib A.M., Andersson D.A., Rash L.D., RA Wood J.N., Zhao J., Stehbens S.J., Mobli M., Leffler A., Jiang D., RA Cox J.J., Waxman S.G., Dib-Hajj S.D., Gregory Neely G., Durek T., RA Vetter I.; RT "Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 RT function."; RL Nat. Commun. 14:2442-2442(2023). RN [26] RP STRUCTURE BY NMR OF 1773-1865, FUNCTION, SUBCELLULAR LOCATION, RESPONSE TO RP CALCIUM, AND MUTAGENESIS OF 1802-ASP--GLU-1804. RX PubMed=19074138; DOI=10.1074/jbc.m807747200; RA Chagot B., Potet F., Balser J.R., Chazin W.J.; RT "Solution NMR structure of the C-terminal EF-hand domain of human cardiac RT sodium channel NaV1.5."; RL J. Biol. Chem. 284:6436-6445(2009). RN [27] RP STRUCTURE BY NMR OF 1901-1927 IN COMPLEX WITH CALM, AND INTERACTION WITH RP CALM. RX PubMed=21167176; DOI=10.1016/j.jmb.2010.11.046; RA Chagot B., Chazin W.J.; RT "Solution NMR structure of Apo-calmodulin in complex with the IQ motif of RT human cardiac sodium channel NaV1.5."; RL J. Mol. Biol. 406:106-119(2011). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1773-1940 IN COMPLEX WITH FGF13 RP AND CALMODULIN. RX PubMed=22705208; DOI=10.1016/j.str.2012.05.001; RA Wang C., Chung B.C., Yan H., Lee S.Y., Pitt G.S.; RT "Crystal structure of the ternary complex of a NaV C-terminal domain, a RT fibroblast growth factor homologous factor, and calmodulin."; RL Structure 20:1167-1176(2012). RN [29] {ECO:0007744|PDB:4OVN} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1773-1929, FUNCTION, SUBCELLULAR RP LOCATION, AND INTERACTION WITH CALMODULIN. RX PubMed=25370050; DOI=10.1038/ncomms6126; RA Gabelli S.B., Boto A., Kuhns V.H., Bianchet M.A., Farinelli F., RA Aripirala S., Yoder J., Jakoncic J., Tomaselli G.F., Amzel L.M.; RT "Regulation of the NaV1.5 cytoplasmic domain by calmodulin."; RL Nat. Commun. 5:5126-5126(2014). RN [30] RP VARIANTS LQT3. RX PubMed=7889574; DOI=10.1016/0092-8674(95)90359-3; RA Wang Q., Shen J., Splawski I., Atkinson D., Li Z., Robinson J.L., RA Moss A.J., Towbin J.A., Keating M.T.; RT "SCN5A mutations associated with an inherited cardiac arrhythmia, long QT RT syndrome."; RL Cell 80:805-811(1995). RN [31] RP VARIANTS LQT3. RX PubMed=8541846; DOI=10.1093/hmg/4.9.1603; RA Wang Q., Shen J., Li Z., Timothy K.W., Vincent G.M., Priori S.G., RA Schwartz P.J., Keating M.T.; RT "Cardiac sodium channel mutations in patients with long QT syndrome, an RT inherited cardiac arrhythmia."; RL Hum. Mol. Genet. 4:1603-1607(1995). RN [32] RP VARIANT LQT3 1505-LYS--GLN-1507 DEL. RX PubMed=7651517; DOI=10.1038/376683a0; RA Bennett P.B., Yazawa K., Makita N., George A.L. Jr.; RT "Molecular mechanism for an inherited cardiac arrhythmia."; RL Nature 376:683-685(1995). RN [33] RP VARIANT LQT3 GLY-1790. RX PubMed=9686753; DOI=10.1161/01.res.83.2.141; RA An R.H., Wang X.L., Kerem B., Benhorin J., Medina A., Goldmit M., RA Kass R.S.; RT "Novel LQT-3 mutation affects Na+ channel activity through interactions RT between alpha- and beta1-subunits."; RL Circ. Res. 83:141-146(1998). RN [34] RP VARIANT LQT3 GLN-1623. RX PubMed=9506831; DOI=10.1016/s0014-5793(98)00033-7; RA Makita N., Shirai N., Nagashima M., Matsuoka R., Yamada Y., Tohse N., RA Kitabatake A.; RT "A de novo missense mutation of human cardiac Na(+) channel exhibiting RT novel molecular mechanisms of long QT syndrome."; RL FEBS Lett. 423:5-9(1998). RN [35] RP VARIANT LQT3 GLY-1839. RX PubMed=10627139; RX DOI=10.1002/(sici)1098-1004(1998)12:1<72::aid-humu19>3.0.co;2-t; RA Benhorin J., Goldmit M., Maccluer J.W., Blangero J., Goffen R., RA Leibovitch A., Rahat A., Wang Q., Medina A., Towbin J.A., Kerem B.; RT "Identification of a new SCN5A mutation, D1840G, associated with the long RT QT syndrome."; RL Hum. Mutat. 12:72-72(1998). RN [36] RP VARIANT LQT3 GLN-1623. RA Yamagishi H., Furutani M., Kamisago M., Morikawa Y., Kojima Y., Hino Y., RA Furutani Y., Kimura M., Imamura S., Takao A., Momma K., Matsuoka R.; RT "A De Novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl RT with sporadic long QT syndrome."; RL Hum. Mutat. 12:481-481(1998). RN [37] RP VARIANTS BRGDA1 TRP-1232 AND MET-1620. RX PubMed=9521325; DOI=10.1038/32675; RA Chen Q., Kirsch G.E., Zhang D., Brugada R., Brugada J., Brugada P., RA Potenza D., Moya A., Borggrefe M., Breithardt G., Ortiz-Lopez R., Wang Z., RA Antzelevitch C., O'Brien R.E., Schulze-Bahr E., Keating M.T., Towbin J.A., RA Wang Q.; RT "Genetic basis and molecular mechanism for idiopathic ventricular RT fibrillation."; RL Nature 392:293-296(1998). RN [38] RP VARIANTS LQT3 MET-1304 AND MET-1645, AND VARIANT ASN-1500. RX PubMed=10508990; RX DOI=10.1002/(sici)1096-8628(19991029)86:5<470::aid-ajmg13>3.0.co;2-y; RA Wattanasirichaigoon D., Vesely M.R., Duggal P., Levine J.C., Blume E.D., RA Wolff G.S., Edwards S.B., Beggs A.H.; RT "Sodium channel abnormalities are infrequent in patients with long QT RT syndrome: identification of two novel SCN5A mutations."; RL Am. J. Med. Genet. 86:470-476(1999). RN [39] RP CHARACTERIZATION OF VARIANTS BRGDA1 TRP-1512 AND THR-1924. RX PubMed=10690282; DOI=10.1016/s0008-6363(99)00350-8; RA Rook M.B., Bezzina Alshinawi C., Groenewegen W.A., van Gelder I.C., RA van Ginneken A.C.G., Jongsma H.J., Mannens M.M.A.M., Wilde A.A.M.; RT "Human SCN5A gene mutations alter cardiac sodium channel kinetics and are RT associated with the Brugada syndrome."; RL Cardiovasc. Res. 44:507-517(1999). RN [40] RP VARIANT LQT3 LYS-1784. RX PubMed=10377081; DOI=10.1161/01.cir.99.24.3165; RA Wei J., Wang D.W., Alings M., Fish F., Wathen M., Roden D.M., RA George A.L. Jr.; RT "Congenital long-QT syndrome caused by a novel mutation in a conserved RT acidic domain of the cardiac Na+ channel."; RL Circulation 99:3165-3171(1999). RN [41] RP CHARACTERIZATION OF VARIANT BRGDA1 MET-1620. RX PubMed=10532948; DOI=10.1161/01.res.85.9.803; RA Dumaine R., Towbin J.A., Brugada P., Vatta M., Nesterenko D.V., RA Nesterenko V.V., Brugada J., Brugada R., Antzelevitch C.; RT "Ionic mechanisms responsible for the electrocardiographic phenotype of the RT Brugada syndrome are temperature dependent."; RL Circ. Res. 85:803-809(1999). RN [42] RP CHARACTERIZATION OF VARIANT LQT3/BRGDA1 ASP-1795 INS. RX PubMed=10590249; DOI=10.1161/01.res.85.12.1206; RA Bezzina C.R., Veldkamp M.W., van Den Berg M.P., Postma A.V., Rook M.B., RA Viersma J.-W., van Langen I.M., Tan-Sindhunata G., Bink-Boelkens M.T.E., RA van Der Hout A.H., Mannens M.M.A.M., Wilde A.A.M.; RT "A single Na(+) channel mutation causing both long-QT and Brugada RT syndromes."; RL Circ. Res. 85:1206-1213(1999). RN [43] RP DISEASE. RX PubMed=10471492; DOI=10.1038/12618; RA Schott J.-J., Alshinawi C., Kyndt F., Probst V., Hoorntje T.M., RA Hulsbeek M., Wilde A.A.M., Escande D., Mannens M.M.A.M., Le Marec H.; RT "Cardiac conduction defects associate with mutations in SCN5A."; RL Nat. Genet. 23:20-21(1999). RN [44] RP CHARACTERIZATION OF VARIANT BRGDA1 MET-1620. RX PubMed=10618304; DOI=10.1161/01.cir.101.1.54; RA Makita N., Shirai N., Wang D.W., Sasaki K., George A.L. Jr., Kanno M., RA Kitabatake A.; RT "Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by RT beta(1)-subunit."; RL Circulation 101:54-60(2000). RN [45] RP VARIANTS LQT3 ASN-1114; VAL-1501; LEU-1623 AND HIS-1644, AND VARIANT RP ASN-1787. RX PubMed=10973849; DOI=10.1161/01.cir.102.10.1178; RA Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S.G., RA Robinson J.L., Moss A.J., Schwartz P.J., Towbin J.A., Vincent G.M., RA Keating M.T.; RT "Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, RT KCNE1, and KCNE2."; RL Circulation 102:1178-1185(2000). RN [46] RP VARIANT VF1 LEU-1710. RX PubMed=10940383; DOI=10.1016/s0014-5793(00)01875-5; RA Akai J., Makita N., Sakurada H., Shirai N., Ueda K., Kitabatake A., RA Nakazawa K., Kimura A., Hiraoka M.; RT "A novel SCN5A mutation associated with idiopathic ventricular fibrillation RT without typical ECG findings of Brugada syndrome."; RL FEBS Lett. 479:29-34(2000). RN [47] RP VARIANT LQT3 ASN-941. RX PubMed=10911008; DOI=10.1056/nejm200007273430405; RA Schwartz P.J., Priori S.G., Dumaine R., Napolitano C., Antzelevitch C., RA Stramba-Badiale M., Richard T.A., Berti M.R., Bloise R.; RT "A molecular link between the sudden infant death syndrome and the long-QT RT syndrome."; RL N. Engl. J. Med. 343:262-267(2000). RN [48] RP VARIANT LQT3 LYS-1295, AND CHARACTERIZATION OF VARIANT LQT3 LYS-1295. RX PubMed=11304498; DOI=10.1161/hh0701.089668; RA Abriel H., Cabo C., Wehrens X.H., Rivolta I., Motoike H.K., Memmi M., RA Napolitano C., Priori S.G., Kass R.S.; RT "Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in RT the cardiac Na(+) channel."; RL Circ. Res. 88:740-745(2001). RN [49] RP CHARACTERIZATION OF VARIANT LQT3 CYS-1795, AND CHARACTERIZATION OF VARIANT RP BRGDA1 HIS-1795. RX PubMed=11410597; DOI=10.1074/jbc.m104471200; RA Rivolta I., Abriel H., Tateyama M., Liu H., Memmi M., Vardas P., RA Napolitano C., Priori S.G., Kass R.S.; RT "Inherited Brugada and long QT-3 syndrome mutations of a single residue of RT the cardiac sodium channel confer distinct channel and clinical RT phenotypes."; RL J. Biol. Chem. 276:30623-30630(2001). RN [50] RP VARIANT SSS1/BRGDA1 ARG-1408. RX PubMed=11748104; DOI=10.1161/hc5001.100834; RA Kyndt F., Probst V., Potet F., Demolombe S., Chevallier J.-C., Baro I., RA Moisan J.-P., Boisseau P., Schott J.-J., Escande D., Le Marec H.; RT "Novel SCN5A mutation leading either to isolated cardiac conduction defect RT or Brugada syndrome in a large French family."; RL Circulation 104:3081-3086(2001). RN [51] RP CHARACTERIZATION OF VARIANTS LQT3 SER-997 AND HIS-1826. RX PubMed=11710892; DOI=10.1001/jama.286.18.2264; RA Ackerman M.J., Siu B.L., Sturner W.Q., Tester D.J., Valdivia C.R., RA Makielski J.C., Towbin J.A.; RT "Postmortem molecular analysis of SCN5A defects in sudden infant death RT syndrome."; RL JAMA 286:2264-2269(2001). RN [52] RP CHARACTERIZATION OF VARIANT PFHB1A CYS-514. RX PubMed=11234013; DOI=10.1038/35059090; RA Tan H.L., Bink-Boelkens M.T.E., Bezzina C.R., Viswanathan P.C., RA Beaufort-Krol G.C.M., van Tintelen P.J., van den Berg M.P., Wilde A.A.M., RA Balser J.R.; RT "A sodium-channel mutation causes isolated cardiac conduction disease."; RL Nature 409:1043-1047(2001). RN [53] RP VARIANTS BRGDA1 LYS-161; CYS-367; LYS-369; ARG-752; LYS-1225; VAL-1319; RP ILE-1382; LEU-1405; ARG-1406; LYS-1479 DEL; SER-1502; TRP-1512; GLU-1743 RP AND THR-1924. RX PubMed=12106943; DOI=10.1016/s0735-1097(02)01962-9; RA Smits J.P.P., Eckardt L., Probst V., Bezzina C.R., Schott J.-J., RA Remme C.A., Haverkamp W., Breithardt G., Escande D., Schulze-Bahr E., RA LeMarec H., Wilde A.A.M.; RT "Genotype-phenotype relationship in Brugada syndrome: electrocardiographic RT features differentiate SCN5A-related patients from non-SCN5A-related RT patients."; RL J. Am. Coll. Cardiol. 40:350-356(2002). RN [54] RP CHARACTERIZATION OF VARIANTS PFHB1A SER-298 AND ASN-1595. RX PubMed=11804990; DOI=10.1161/hc0302.102592; RA Wang D.W., Viswanathan P.C., Balser J.R., George A.L. Jr., Benson D.W.; RT "Clinical, genetic and biophysical characterisation of SCN5A mutations RT associated with atrioventricular conduction block."; RL Circulation 105:341-346(2002). RN [55] RP MODELING OF VARIANT LQT3/BRGDA1 ASP-1795 INS. RX PubMed=11889015; DOI=10.1161/hc1002.105183; RA Clancy C.E., Rudy Y.; RT "Na(+) channel mutation that causes both Brugada and long-QT syndrome RT phenotypes: a simulation study of mechanism."; RL Circulation 105:1208-1213(2002). RN [56] RP VARIANTS BRGDA1 HIS-27; VAL-226; VAL-230; HIS-282; MET-294; SER-319; RP PHE-393 DEL; GLN-567; PRO-681; GLU-735; LEU-851; ILE-892; SER-896; LEU-910; RP CYS-965; LYS-1053; ASN-1236; SER-1293; LYS-1500 DEL; ARG-1740; LYS-1784; RP HIS-1795 AND LEU-1951, AND VARIANT GLN-1240. RX PubMed=11901046; DOI=10.1161/hc1102.105288; RA Priori S.G., Napolitano C., Gasparini M., Pappone C., Della Bella P., RA Giordano U., Bloise R., Giustetto C., De Nardis R., Grillo M., RA Ronchetti E., Faggiano G., Nastoli J.; RT "Natural history of Brugada syndrome: insights for risk stratification and RT management."; RL Circulation 105:1342-1347(2002). RN [57] RP VARIANTS LQT3 GLU-615; PHE-619 AND LEU-1250, AND VARIANTS CYS-34 AND RP ARG-558. RX PubMed=11997281; DOI=10.1161/01.cir.0000014448.19052.4c; RA Yang P., Kanki H., Drolet B., Yang T., Wei J., Viswanathan P.C., RA Hohnloser S.H., Shimizu W., Schwartz P.J., Stanton M., Murray K.T., RA Norris K., George A.L. Jr., Roden D.M.; RT "Allelic variants in long-QT disease genes in patients with drug-associated RT torsades de pointes."; RL Circulation 105:1943-1948(2002). RN [58] RP CHARACTERIZATION OF VARIANTS BRGDA1 HIS-367; VAL-735 AND GLN-1193. RX PubMed=11823453; DOI=10.1093/hmg/11.3.337; RA Vatta M., Dumaine R., Varghese G., Richard T.A., Shimizu W., Aihara N., RA Nademanee K., Brugada R., Brugada J., Veerakul G., Li H., Bowles N.E., RA Brugada P., Antzelevitch C., Towbin J.A.; RT "Genetic and biophysical basis of sudden unexplained nocturnal death RT syndrome (SUNDS), a disease allelic to Brugada syndrome."; RL Hum. Mol. Genet. 11:337-345(2002). RN [59] RP VARIANT TYR-1103. RX PubMed=12471205; DOI=10.1136/jmg.39.12.913; RA Chen S., Chung M.K., Martin D., Rozich R., Tchou P.J., Wang Q.; RT "SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with RT cardiac arrhythmias and sudden death in a white family."; RL J. Med. Genet. 39:913-915(2002). RN [60] RP VARIANTS BRGDA1 GLU-126 AND VAL-351, CHARACTERIZATION OF VARIANT BRGDA1 RP VAL-351, AND VARIANT ARG-558. RX PubMed=12051963; DOI=10.1016/s1096-7192(02)00006-9; RA Vatta M., Dumaine R., Antzelevitch C., Brugada R., Li H., Bowles N.E., RA Nademanee K., Brugada J., Brugada P., Towbin J.A.; RT "Novel mutations in domain I of SCN5A cause Brugada syndrome."; RL Mol. Genet. Metab. 75:317-324(2002). RN [61] RP VARIANT LQT3 VAL-1768, AND CHARACTERIZATION OF VARIANT LQT3 VAL-1768. RX PubMed=12209021; DOI=10.1152/physiolgenomics.00039.2002; RA Rivolta I., Clancy C.E., Tateyama M., Liu H., Priori S.G., Kass R.S.; RT "A novel SCN5A mutation associated with long QT-3: altered inactivation RT kinetics and channel dysfunction."; RL Physiol. Genomics 10:191-197(2002). RN [62] RP VARIANT TYR-1103. RX PubMed=12193783; DOI=10.1126/science.1073569; RA Splawski I., Timothy K.W., Tateyama M., Clancy C.E., Malhotra A., RA Beggs A.H., Cappuccio F.P., Sagnella G.A., Kass R.S., Keating M.T.; RT "Variant of SCN5A sodium channel implicated in risk of cardiac RT arrhythmia."; RL Science 297:1333-1336(2002). RN [63] RP VARIANT ATRST1 ASN-1275. RX PubMed=12522116; DOI=10.1161/01.res.0000050585.07097.d7; RA Groenewegen W.A., Firouzi M., Bezzina C.R., Vliex S., van Langen I.M., RA Sandkuijl L., Smits J.P., Hulsbeek M., Rook M.B., Jongsma H.J., RA Wilde A.A.M.; RT "A cardiac sodium channel mutation cosegregates with a rare connexin40 RT genotype in familial atrial standstill."; RL Circ. Res. 92:14-22(2003). RN [64] RP VARIANT PFHB1A TRP-225. RX PubMed=12574143; DOI=10.1161/01.res.0000052672.97759.36; RA Bezzina C.R., Rook M.B., Groenewegen W.A., Herfst L.J., van der Wal A.C., RA Lam J., Jongsma H.J., Wilde A.A.M., Mannens M.M.; RT "Compound heterozygosity for mutations (W156X and R225W) in SCN5A RT associated with severe cardiac conduction disturbances and degenerative RT changes in the conduction system."; RL Circ. Res. 92:159-168(2003). RN [65] RP VARIANT LQT3 PHE-619. RX PubMed=12673799; DOI=10.1002/humu.9136; RA Wehrens X.H., Rossenbacker T., Jongbloed R.J., Gewillig M., Heidbuchel H., RA Doevendans P.A., Vos M.A., Wellens H.J., Kass R.S.; RT "A novel mutation L619F in the cardiac Na+ channel SCN5A associated with RT long-QT syndrome (LQT3): a role for the I-II linker in inactivation RT gating."; RL Hum. Mutat. 21:552-552(2003). RN [66] RP VARIANT PFHB1A ILE-512, CHARACTERIZATION OF VARIANT PFHB1A ILE-512, VARIANT RP ARG-558, AND CHARACTERIZATION OF VARIANT ARG-558. RX PubMed=12569159; DOI=10.1172/jci16879; RA Viswanathan P.C., Benson D.W., Balser J.R.; RT "A common SCN5A polymorphism modulates the biophysical effects of an SCN5A RT mutation."; RL J. Clin. Invest. 111:341-346(2003). RN [67] RP VARIANTS SSS1 ILE-220; LEU-1298 AND ARG-1408. RX PubMed=14523039; DOI=10.1172/jci18062; RA Benson D.W., Wang D.W., Dyment M., Knilans T.K., Fish F.A., Strieper M.J., RA Rhodes T.H., George A.L. Jr.; RT "Congenital sick sinus syndrome caused by recessive mutations in the RT cardiac sodium channel gene (SCN5A)."; RL J. Clin. Invest. 112:1019-1028(2003). RN [68] RP VARIANT BRGDA1 ARG-1743, AND CHARACTERIZATION OF VARIANT BRGDA1 ARG-1743. RX PubMed=15023552; DOI=10.1016/j.cardiores.2004.01.022; RA Valdivia C.R., Tester D.J., Rok B.A., Porter C.B., Munger T.M., RA Jahangir A., Makielski J.C., Ackerman M.J.; RT "A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued RT by drugs."; RL Cardiovasc. Res. 62:53-62(2004). RN [69] RP VARIANT CMD1E ASN-1275. RX PubMed=15466643; DOI=10.1161/01.cir.0000144458.58660.bb; RG The familial cardiomyopathy registry research group; RA McNair W.P., Ku L., Taylor M.R.G., Fain P.R., Dao D., Wolfel E., RA Mestroni L.; RT "SCN5A mutation associated with dilated cardiomyopathy, conduction RT disorder, and arrhythmia."; RL Circulation 110:2163-2167(2004). RN [70] RP VARIANT BRGDA1 SER-1262. RX PubMed=15338453; DOI=10.1007/s10038-004-0182-z; RA Shin D.-J., Jang Y., Park H.-Y., Lee J.E., Yang K., Kim E., Bae Y., Kim J., RA Kim J., Kim S.S., Lee M.H., Chahine M., Yoon S.K.; RT "Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with RT Brugada syndrome."; RL J. Hum. Genet. 49:573-578(2004). RN [71] RP VARIANT BRGDA1 LYS-1053, CHARACTERIZATION OF VARIANT BRGDA1 LYS-1053, AND RP INTERACTION WITH ANK3. RX PubMed=15579534; DOI=10.1073/pnas.0403711101; RA Mohler P.J., Rivolta I., Napolitano C., LeMaillet G., Lambert S., RA Priori S.G., Bennett V.; RT "Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin- RT G and expression of Nav1.5 on the surface of cardiomyocytes."; RL Proc. Natl. Acad. Sci. U.S.A. 101:17533-17538(2004). RN [72] RP VARIANT BRGDA1 GLY-1714, AND CHARACTERIZATION OF VARIANT BRGDA1 GLY-1714. RX PubMed=16266370; DOI=10.1111/j.1365-201x.2005.01496.x; RA Amin A.S., Verkerk A.O., Bhuiyan Z.A., Wilde A.A.M., Tan H.L.; RT "Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac RT Na+ channel does not affect ion selectivity properties."; RL Acta Physiol. Scand. 185:291-301(2005). RN [73] RP VARIANTS BRGDA1 ARG-1527 AND PRO-1569. RX PubMed=15851320; DOI=10.1016/j.hrthm.2004.11.022; RA Yokoi H., Makita N., Sasaki K., Takagi Y., Okumura Y., Nishino T., RA Makiyama T., Kitabatake A., Horie M., Watanabe I., Tsutsui H.; RT "Double SCN5A mutation underlying asymptomatic Brugada syndrome."; RL Heart Rhythm 2:285-292(2005). RN [74] RP VARIANTS LQT3 GLU-413; THR-413; GLU-573; ARG-579; HIS-689; PRO-1626; RP CYS-1644; VAL-1660; CYS-1767; GLY-1790 AND HIS-1913, AND VARIANTS THR-1498 RP AND ASN-1787. RX PubMed=16414944; DOI=10.1001/jama.294.23.2975; RA Napolitano C., Priori S.G., Schwartz P.J., Bloise R., Ronchetti E., RA Nastoli J., Bottelli G., Cerrone M., Leonardi S.; RT "Genetic testing in the long QT syndrome: development and validation of an RT efficient approach to genotyping in clinical practice."; RL JAMA 294:2975-2980(2005). RN [75] RP VARIANTS LQT3 LEU-125; LYS-245; GLN-404; LYS-406; MET-411; LYS-462; RP ASP-572; GLU-615; LEU-637; LEU-648; CYS-971; MET-1069; LYS-1225; LYS-1231; RP SER-1325; TYR-1458; GLU-1481; 1505-LYS--GLN-1507 DEL; LEU-1623; HIS-1644; RP ILE-1667; MET-1763; LEU-1766; MET-1777; MET-1779; LYS-1784; CYS-1795; RP ARG-1909 AND SER-1949, AND VARIANTS TRP-18; PHE-618 AND GLN-1958. RX PubMed=15840476; DOI=10.1016/j.hrthm.2005.01.020; RA Tester D.J., Will M.L., Haglund C.M., Ackerman M.J.; RT "Compendium of cardiac channel mutations in 541 consecutive unrelated RT patients referred for long QT syndrome genetic testing."; RL Heart Rhythm 2:507-517(2005). RN [76] RP VARIANTS BRGDA1 ILE-187 AND ASN-356, AND CHARACTERIZATION OF VARIANTS RP BRGDA1 ILE-187 AND ASN-356. RX PubMed=16325048; DOI=10.1016/j.jacc.2005.08.043; RA Makiyama T., Akao M., Tsuji K., Doi T., Ohno S., Takenaka K., Kobori A., RA Ninomiya T., Yoshida H., Takano M., Makita N., Yanagisawa F., Higashi Y., RA Takeyama Y., Kita T., Horie M.; RT "High risk for bradyarrhythmic complications in patients with Brugada RT syndrome caused by SCN5A gene mutations."; RL J. Am. Coll. Cardiol. 46:2100-2106(2005). RN [77] RP VARIANT BRGDA1 SER-1344, AND VARIANTS ARG-552 AND GLN-1027. RX PubMed=16616735; DOI=10.1016/j.cardiores.2006.02.030; RA Keller D.I., Huang H., Zhao J., Frank R., Suarez V., Delacretaz E., RA Brink M., Osswald S., Schwick N., Chahine M.; RT "A novel SCN5A mutation, F1344S, identified in a patient with Brugada RT syndrome and fever-induced ventricular fibrillation."; RL Cardiovasc. Res. 70:521-529(2006). RN [78] RP VARIANTS BRGDA1 LEU-336 AND VAL-1660, AND CHARACTERIZATION OF VARIANTS RP BRGDA1 LEU-336 AND VAL-1660. RX PubMed=17075016; DOI=10.1161/circulationaha.106.627489; RA Cordeiro J.M., Barajas-Martinez H., Hong K., Burashnikov E., Pfeiffer R., RA Orsino A.M., Wu Y.S., Hu D., Brugada J., Brugada P., Antzelevitch C., RA Dumaine R., Brugada R.; RT "Compound heterozygous mutations P336L and I1660V in the human cardiac RT sodium channel associated with the Brugada syndrome."; RL Circulation 114:2026-2033(2006). RN [79] RP VARIANTS LQT3 VAL-9; GLN-225; ARG-639; TYR-1333; TRP-1609 AND ASN-1819. RX PubMed=16922724; DOI=10.1111/j.1399-0004.2006.00671.x; RA Millat G., Chevalier P., Restier-Miron L., Da Costa A., Bouvagnet P., RA Kugener B., Fayol L., Gonzalez Armengod C., Oddou B., Chanavat V., RA Froidefond E., Perraudin R., Rousson R., Rodriguez-Lafrasse C.; RT "Spectrum of pathogenic mutations and associated polymorphisms in a cohort RT of 44 unrelated patients with long QT syndrome."; RL Clin. Genet. 70:214-227(2006). RN [80] RP VARIANTS BRGDA1 ILE-95; PHE-1617 DEL AND VAL-1649. RX PubMed=17081365; RA Liang P., Liu W.L., Hu D.Y., Li C.L., Tao W.H., Li L.; RT "Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V RT and delF1617."; RL Zhonghua Xin Xue Guan Bing Za Zhi 34:616-619(2006). RN [81] RP VARIANT LQT3 LEU-1904, AND CHARACTERIZATION OF VARIANT LQT3 LEU-1904. RX PubMed=18708744; DOI=10.4161/chan.4956; RA Bankston J.R., Sampson K.J., Kateriya S., Glaaser I.W., Malito D.L., RA Chung W.K., Kass R.S.; RT "A novel LQT-3 mutation disrupts an inactivation gate complex with distinct RT rate-dependent phenotypic consequences."; RL Channels 1:273-280(2007). RN [82] RP VARIANT BRGDA1 ILE-353. RX PubMed=17198989; DOI=10.1016/j.hrthm.2006.09.031; RA Pfahnl A.E., Viswanathan P.C., Weiss R., Shang L.L., Sanyal S., RA Shusterman V., Kornblit C., London B., Dudley S.C. Jr.; RT "A sodium channel pore mutation causing Brugada syndrome."; RL Heart Rhythm 4:46-53(2007). RN [83] RP VARIANT LQT3 CYS-1473. RX PubMed=18060054; DOI=10.1371/journal.pone.0001258; RA Bankston J.R., Yue M., Chung W., Spyres M., Pass R.H., Silver E., RA Sampson K.J., Kass R.S.; RT "A novel and lethal de novo LQT-3 mutation in a newborn with distinct RT molecular pharmacology and therapeutic response."; RL PLoS ONE 2:E1258-E1258(2007). RN [84] RP VARIANT BRGDA1 ASN-1494. RX PubMed=18341814; RA Tian L., Zhu J.F., Yang J.G.; RT "Gene (SCN5A) mutation analysis of a Chinese family with Brugada RT syndrome."; RL Zhonghua Xin Xue Guan Bing Za Zhi 35:1122-1125(2007). RN [85] RP VARIANT BRGDA1 CYS-878. RX PubMed=18616619; DOI=10.1111/j.1748-1716.2008.01883.x; RA Zhang Y., Wang T., Ma A., Zhou X., Gui J., Wan H., Shi R., Huang C., RA Grace A.A., Huang C.L., Trump D., Zhang H., Zimmer T., Lei M.; RT "Correlations between clinical and physiological consequences of the novel RT mutation R878C in a highly conserved pore residue in the cardiac Na+ RT channel."; RL Acta Physiol. 194:311-323(2008). RN [86] RP VARIANT BRGDA1 LEU-2004, AND CHARACTERIZATION OF VARIANT BRGDA1 LEU-2004. RX PubMed=18456723; DOI=10.1152/ajpheart.91495.2007; RA Bebarova M., O'Hara T., Geelen J.L.M.C., Jongbloed R.J., Timmermans C., RA Arens Y.H., Rodriguez L.-M., Rudy Y., Volders P.G.A.; RT "Subepicardial phase 0 block and discontinuous transmural conduction RT underlie right precordial ST-segment elevation by a SCN5A loss-of-function RT mutation."; RL Am. J. Physiol. 295:H48-H58(2008). RN [87] RP VARIANT BRGDA1 SER-1850, AND CHARACTERIZATION OF VARIANT BRGDA1 SER-1850. RX PubMed=18252757; DOI=10.1093/cvr/cvn023; RA Petitprez S., Jespersen T., Pruvot E., Keller D.I., Corbaz C., RA Schlapfer J., Abriel H., Kucera J.P.; RT "Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization RT disorder hypotheses in the Brugada syndrome."; RL Cardiovasc. Res. 78:494-504(2008). RN [88] RP VARIANTS ILE-232 AND PHE-1308. RX PubMed=18599870; DOI=10.1161/circresaha.108.172619; RA Barajas-Martinez H.M., Hu D., Cordeiro J.M., Wu Y., Kovacs R.J., RA Meltser H., Kui H., Elena B., Brugada R., Antzelevitch C., Dumaine R.; RT "Lidocaine-induced Brugada syndrome phenotype linked to a novel double RT mutation in the cardiac sodium channel."; RL Circ. Res. 103:396-404(2008). RN [89] RP VARIANTS ATFB10 ILE-138; LEU-216; HIS-376; LYS-428; ASP-445; LYS-470; RP ASP-572; LYS-655; LYS-1053; ILE-1131; CYS-1826 AND MET-1951, VARIANTS RP CYS-34; VAL-461; TRP-481; TYR-524; ARG-558; PHE-618; SER-997 AND TYR-1103, RP AND VARIANTS LQT3 GLN-1193; LEU-1951 AND LEU-2004. RX PubMed=18378609; DOI=10.1161/circulationaha.107.757955; RA Darbar D., Kannankeril P.J., Donahue B.S., Kucera G., Stubblefield T., RA Haines J.L., George A.L. Jr., Roden D.M.; RT "Cardiac sodium channel (SCN5A) variants associated with atrial RT fibrillation."; RL Circulation 117:1927-1935(2008). RN [90] RP VARIANT ATFB10 LYS-1987. RX PubMed=18088563; DOI=10.1016/j.hrthm.2007.09.015; RA Ellinor P.T., Nam E.G., Shea M.A., Milan D.J., Ruskin J.N., MacRae C.A.; RT "Cardiac sodium channel mutation in atrial fibrillation."; RL Heart Rhythm 5:99-105(2008). RN [91] RP VARIANT LQT3 CYS-1795. RX PubMed=18929331; DOI=10.1016/j.hrthm.2008.07.013; RA Benito B., Brugada R., Perich R.M., Lizotte E., Cinca J., Mont L., RA Berruezo A., Tolosana J.M., Freixa X., Brugada P., Brugada J.; RT "A mutation in the sodium channel is responsible for the association of RT long QT syndrome and familial atrial fibrillation."; RL Heart Rhythm 5:1434-1440(2008). RN [92] RP VARIANT LQT3 GLN-43, AND CHARACTERIZATION OF VARIANT LQT3 GLN-43. RX PubMed=18848812; DOI=10.1016/j.hrthm.2008.08.010; RA Lin M.-T., Wu M.-H., Chang C.-C., Chiu S.-N., Theriault O., Huang H., RA Christe G., Ficker E., Chahine M.; RT "In utero onset of long QT syndrome with atrioventricular block and RT spontaneous or lidocaine-induced ventricular tachycardia: compound effects RT of hERG pore region mutation and SCN5A N-terminus variant."; RL Heart Rhythm 5:1567-1574(2008). RN [93] RP VARIANT ATRIAL FIBRILLATION THR-1875, AND CHARACTERIZATION OF VARIANT RP ATRIAL FIBRILLATION THR-1875. RX PubMed=18929244; DOI=10.1016/j.jacc.2008.07.013; RA Makiyama T., Akao M., Shizuta S., Doi T., Nishiyama K., Oka Y., Ohno S., RA Nishio Y., Tsuji K., Itoh H., Kimura T., Kita T., Horie M.; RT "A novel SCN5A gain-of-function mutation M1875T associated with familial RT atrial fibrillation."; RL J. Am. Coll. Cardiol. 52:1326-1334(2008). RN [94] RP VARIANT LQT3/BRGDA1/SSS1 LYS-1784. RX PubMed=18451998; DOI=10.1172/jci34057; RA Makita N., Behr E., Shimizu W., Horie M., Sunami A., Crotti L., RA Schulze-Bahr E., Fukuhara S., Mochizuki N., Makiyama T., Itoh H., RA Christiansen M., McKeown P., Miyamoto K., Kamakura S., Tsutsui H., RA Schwartz P.J., George A.L. Jr., Roden D.M.; RT "The E1784K mutation in SCN5A is associated with mixed clinical phenotype RT of type 3 long QT syndrome."; RL J. Clin. Invest. 118:2219-2229(2008). RN [95] RP VARIANTS ARG-558 AND LEU-1090. RX PubMed=18368697; DOI=10.1016/j.ymgme.2007.10.009; RA Shan L., Makita N., Xing Y., Watanabe S., Futatani T., Ye F., Saito K., RA Ibuki K., Watanabe K., Hirono K., Uese K., Ichida F., Miyawaki T., RA Origasa H., Bowles N.E., Towbin J.A.; RT "SCN5A variants in Japanese patients with left ventricular noncompaction RT and arrhythmia."; RL Mol. Genet. Metab. 93:468-474(2008). RN [96] RP VARIANTS SIDS CYS-532; SER-1084 AND SER-1705, AND CHARACTERIZATION OF RP VARIANT SIDS SER-1705. RX PubMed=18596570; DOI=10.1203/pdr.0b013e3181841eca; RA Otagiri T., Kijima K., Osawa M., Ishii K., Makita N., Matoba R., Umetsu K., RA Hayasaka K.; RT "Cardiac ion channel gene mutations in sudden infant death syndrome."; RL Pediatr. Res. 64:482-487(2008). RN [97] RP VARIANT IRRITABLE BOWEL SYNDROME SER-298, AND CHARACTERIZATION OF VARIANT RP IRRITABLE BOWEL SYNDROME SER-298. RX PubMed=19056759; DOI=10.1152/ajpgi.90571.2008; RA Saito Y.A., Strege P.R., Tester D.J., Locke G.R. III, Talley N.J., RA Bernard C.E., Rae J.L., Makielski J.C., Ackerman M.J., Farrugia G.; RT "Sodium channel mutation in irritable bowel syndrome: evidence for an ion RT channelopathy."; RL Am. J. Physiol. 296:G211-G218(2009). RN [98] RP VARIANT SIDS TYR-1333. RX PubMed=19302788; DOI=10.1016/j.febslet.2009.02.007; RA Huang H., Millat G., Rodriguez-Lafrasse C., Rousson R., Kugener B., RA Chevalier P., Chahine M.; RT "Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS RT infant linked to long QT syndrome."; RL FEBS Lett. 583:890-896(2009). RN [99] RP VARIANTS BRGDA1 LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; TRP-1232; RP ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; GLU-1743 AND RP THR-1924, AND VARIANTS PFHB1A LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; RP TRP-1232; ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; RP GLU-1743 AND THR-1924. RX PubMed=19251209; DOI=10.1016/j.hrthm.2008.11.009; RA Meregalli P.G., Tan H.L., Probst V., Koopmann T.T., Tanck M.W., RA Bhuiyan Z.A., Sacher F., Kyndt F., Schott J.-J., Albuisson J., Mabo P., RA Bezzina C.R., Le Marec H., Wilde A.A.M.; RT "Type of SCN5A mutation determines clinical severity and degree of RT conduction slowing in loss-of-function sodium channelopathies."; RL Heart Rhythm 6:341-348(2009). RN [100] RP VARIANTS LQT3 GLN-18; HIS-27; GLY-30; GLN-43; LYS-48; SER-52; GLN-53; RP GLY-104; GLY-115; LEU-125; PRO-212; GLN-222; TRP-225; MET-240; LEU-247; RP LYS-275; SER-289; TRP-340; CYS-367; MET-370; THR-397; LYS-406; VAL-409; RP MET-411; GLU-429 DEL; ALA-462; VAL-530; GLN-535; TRP-569; ILE-571; SER-572; RP VAL-572; 586-ALA-LEU-587 DEL; GLU-615; ARG-639; LYS-654; PRO-673; CYS-689; RP LEU-701; ILE-731; ARG-750; ASN-772; TYR-816; PHE-848; LYS-960; LEU-965; RP PHE-981; SER-997; ARG-1004; LYS-1053; MET-1069; VAL-1100; ASN-1114; RP ASN-1166; SER-1199; ILE-1212 DEL; MET-1283; MET-1304; SER-1325; SER-1326; RP VAL-1334; VAL-1338; SER-1432; SER-1472; CYS-1473; GLU-1481; LEU-1487; RP ARG-1488; ASP-1489; ARG-1493; SER-1495; VAL-1498; VAL-1501; ASN-1505; RP ILE-1532; PHE-1560; MET-1593; SER-1594; ILE-1596; PHE-1617 DEL; GLN-1623; RP LEU-1623; HIS-1626; CYS-1644; PHE-1650; THR-1652; ASN-1723; TRP-1739; RP HIS-1761; PHE-1761; MET-1763; MET-1777; MET-1779; LYS-1784; CYS-1795; RP HIS-1826; GLY-1839; TRP-1897; GLN-1901; ASN-1977; VAL-2004 AND CYS-2012. RX PubMed=19716085; DOI=10.1016/j.hrthm.2009.05.021; RA Kapplinger J.D., Tester D.J., Salisbury B.A., Carr J.L., Harris-Kerr C., RA Pollevick G.D., Wilde A.A., Ackerman M.J.; RT "Spectrum and prevalence of mutations from the first 2,500 consecutive RT unrelated patients referred for the FAMILION long QT syndrome genetic RT test."; RL Heart Rhythm 6:1297-1303(2009). RN [101] RP VARIANT BRGDA1 CYS-965, AND CHARACTERIZATION OF VARIANT BRGDA1 CYS-965. RX PubMed=19272188; DOI=10.1186/1423-0127-16-23; RA Hsueh C.H., Chen W.P., Lin J.L., Tsai C.T., Liu Y.B., Juang J.M., RA Tsao H.M., Su M.J., Lai L.P.; RT "Distinct functional defect of three novel Brugada syndrome related cardiac RT sodium channel mutations."; RL J. Biomed. Sci. 16:23-23(2009). RN [102] RP VARIANTS TRP-18; CYS-34; HIS-34; SER-286; SER-291; MET-299; CYS-376; RP GLY-447; ALA-449; VAL-461; SER-475; TRP-481; TYR-524; ARG-558; HIS-568; RP ARG-579; LYS-592; GLY-596; ALA-601; PHE-618; ASP-638; LEU-656; THR-672; RP HIS-689; LYS-692; PHE-705; ILE-924; GLN-986; MET-1016; ARG-1040; ALA-1082; RP LEU-1090; LEU-1098; TYR-1103; LYS-1107; TRP-1116; GLN-1193; MET-1251; RP SER-1293; PHE-1308; TRP-1512; ASN-1787; THR-1836; LYS-1901; CYS-1919; RP LEU-1951; GLN-1958; LEU-1962; MET-1968; GLN-1991; LEU-2004 AND ALA-2006, RP AND VARIANTS BRGDA1 GLN-18; LYS-70; ASN-84; SER-93; SER-94; GLN-104; RP TRP-104; LYS-109; GLN-121; TRP-121; GLU-126; PRO-136; MET-146; GLN-161; RP LYS-161; ASN-175; GLY-178; ARG-182; VAL-185; VAL-204; GLN-212; LEU-216; RP ILE-220; GLN-222; LEU-223; TRP-225; VAL-226; ILE-232; MET-240; LYS-270; RP GLN-276; ASP-278; CYS-282; ILE-300; PRO-315; ASN-320; ARG-325; LEU-336; RP ASP-351; VAL-351; ASN-356; CYS-367; HIS-367; LEU-367; LYS-369; GLY-374; RP HIS-376; ARG-386; GLU-386; ALA-396; LEU-396; LYS-439; GLY-501; HIS-526; RP CYS-532; LEU-543; ARG-552; GLU-615; PHE-619; CYS-620; MET-632; ALA-640; RP ASP-647; LEU-648; TRP-661; GLY-683; LEU-701; LEU-717; VAL-735; LYS-746; RP ARG-752; GLU-758; ARG-764; ASN-772; SER-773; ILE-789; PRO-808; PRO-839; RP LEU-851; GLN-867; CYS-878; HIS-878; PRO-886; CYS-893; HIS-893; LYS-901; RP LEU-910; ARG-915; ARG-917; SER-927; PRO-928; PRO-935; CYS-965; HIS-965; RP THR-997; LYS-1053; GLY-1055; TYR-1079; VAL-1113; THR-1140; ASN-1219; RP LYS-1225; HIS-1228; GLN-1232; TRP-1232; PRO-1239; ASN-1243; ASP-1249; RP GLY-1253; SER-1262; CYS-1271; ASN-1275; GLY-1288; PRO-1311; VAL-1319; RP GLY-1323; LEU-1332; LEU-1344; ILE-1346; PRO-1346; ARG-1351; MET-1353; RP TRP-1358; ASN-1359; CYS-1360; TYR-1363; ILE-1382; LEU-1405; MET-1405; RP ARG-1406; GLU-1406; ARG-1408; CYS-1409; PHE-1412; GLU-1419; ARG-1420; RP SER-1427; VAL-1428; GLY-1432; SER-1432; VAL-1433; LEU-1438; GLN-1441; RP LEU-1448; THR-1448; CYS-1449; ASP-1451; TYR-1463; PHE-1468; VAL-1501; RP LYS-1521; MET-1525; LYS-1548; CYS-1571; LYS-1574; PRO-1582; CYS-1583; RP HIS-1583; MET-1604; LEU-1613; MET-1620; GLN-1623; GLN-1629; GLU-1642; RP VAL-1660; ARG-1661; ILE-1667; TYR-1672; THR-1680; THR-1698; ARG-1709; RP MET-1709; SER-1712; GLY-1714; ASP-1722; ARG-1728; TRP-1728; ARG-1740; RP ARG-1743; GLU-1743; PHE-1764; MET-1779; LYS-1784; GLU-1832; ILE-1861; RP ASN-1872; LEU-1903; THR-1924; SER-1935; LYS-1938 AND VAL-2004. RX PubMed=20129283; DOI=10.1016/j.hrthm.2009.09.069; RA Kapplinger J.D., Tester D.J., Alders M., Benito B., Berthet M., Brugada J., RA Brugada P., Fressart V., Guerchicoff A., Harris-Kerr C., Kamakura S., RA Kyndt F., Koopmann T.T., Miyamoto Y., Pfeiffer R., Pollevick G.D., RA Probst V., Zumhagen S., Vatta M., Towbin J.A., Shimizu W., Schulze-Bahr E., RA Antzelevitch C., Salisbury B.A., Guicheney P., Wilde A.A., Brugada R., RA Schott J.J., Ackerman M.J.; RT "An international compendium of mutations in the SCN5A-encoded cardiac RT sodium channel in patients referred for Brugada syndrome genetic testing."; RL Heart Rhythm 7:33-46(2010). RN [103] RP CHARACTERIZATION OF VARIANTS ARG-558 AND ALA-2006. RX PubMed=21109022; DOI=10.1016/j.hrthm.2010.11.034; RA Shinlapawittayatorn K., Du X.X., Liu H., Ficker E., Kaufman E.S., RA Deschenes I.; RT "A common SCN5A polymorphism modulates the biophysical defects of SCN5A RT mutations."; RL Heart Rhythm 8:455-462(2011). RN [104] RP VARIANTS SSS1 VAL-735 AND ASN-1792. RX PubMed=22795782; DOI=10.1016/j.arcped.2012.04.017; RA Selly J.B., Boumahni B., Edmar A., Jamal Bey K., Randrianaivo H., RA Clerici G., Millat G., Caillet D.; RT "Cardiac sinus node dysfunction due to a new mutation of the SCN5A gene."; RL Arch. Pediatr. 19:837-841(2012). RN [105] RP VARIANT ARG-558, VARIANTS BRGDA1 ASN-1690 AND ASP-1748, CHARACTERIZATION OF RP VARIANTS BRGDA1 ASN-1690 AND ASP-1748, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=23085483; DOI=10.1016/j.hrthm.2012.10.025; RA Nunez L., Barana A., Amoros I., de la Fuente M.G., Dolz-Gaiton P., RA Gomez R., Rodriguez-Garcia I., Mosquera I., Monserrat L., Delpon E., RA Caballero R., Castro-Beiras A., Tamargo J.; RT "p.D1690N Nav1.5 rescues p.G1748D mutation gating defects in a compound RT heterozygous Brugada syndrome patient."; RL Heart Rhythm 10:264-272(2013). RN [106] RP VARIANT BRGDA1 GLN-1629, CHARACTERIZATION OF VARIANT BRGDA1 GLN-1629, AND RP FUNCTION. RX PubMed=24167619; DOI=10.1371/journal.pone.0078382; RA Zeng Z., Zhou J., Hou Y., Liang X., Zhang Z., Xu X., Xie Q., Li W., RA Huang Z.; RT "Electrophysiological characteristics of a SCN5A voltage sensors mutation RT R1629Q associated with Brugada syndrome."; RL PLoS ONE 8:E78382-E78382(2013). RN [107] RP VARIANT BRGDA1 GLN-812, CHARACTERIZATION OF VARIANT BRGDA1 GLN-812, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26279430; DOI=10.1159/000430189; RA Wang L., Meng X., Yuchi Z., Zhao Z., Xu D., Fedida D., Wang Z., Huang C.; RT "De novo mutation in the SCN5A gene associated with brugada syndrome."; RL Cell. Physiol. Biochem. 36:2250-2262(2015). RN [108] RP VARIANT LQT3 ARG-1849, CHARACTERIZATION OF VARIANT LQT3 ARG-1849, FUNCTION, RP AND INTERACTION WITH FGF12; FGF13 AND FGF14. RX PubMed=26392562; DOI=10.1073/pnas.1516430112; RA Musa H., Kline C.F., Sturm A.C., Murphy N., Adelman S., Wang C., Yan H., RA Johnson B.L., Csepe T.A., Kilic A., Higgins R.S., Janssen P.M., RA Fedorov V.V., Weiss R., Salazar C., Hund T.J., Pitt G.S., Mohler P.J.; RT "SCN5A variant that blocks fibroblast growth factor homologous factor RT regulation causes human arrhythmia."; RL Proc. Natl. Acad. Sci. U.S.A. 112:12528-12533(2015). RN [109] RP VARIANT BRGDA1 GLU-817, CHARACTERIZATION OF VARIANT BRGDA1 GLU-817, AND RP FUNCTION. RX PubMed=26776555; DOI=10.1016/j.hrthm.2016.01.008; RA Kinoshita K., Takahashi H., Hata Y., Nishide K., Kato M., Fujita H., RA Yoshida S., Murai K., Mizumaki K., Nishida K., Yamaguchi Y., Kano M., RA Tabata T., Nishida N.; RT "SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the RT activation gating of NaV1.5 channel."; RL Heart Rhythm 13:1113-1120(2016). RN [110] RP VARIANT BRGDA1 LEU-1571, AND CHARACTERIZATION OF VARIANT BRGDA1 LEU-1571. RX PubMed=32850980; DOI=10.3389/fcvm.2020.00117; RA Nijak A., Labro A.J., De Wilde H., Dewals W., Peigneur S., Tytgat J., RA Snyders D., Sieliwonczyk E., Simons E., Van Craenenbroeck E., Schepers D., RA Van Laer L., Saenen J., Loeys B., Alaerts M.; RT "Compound heterozygous SCN5A mutations in severe sodium channelopathy with RT Brugada syndrome: a case report."; RL Front. Cardiovasc. Med. 7:117-117(2020). CC -!- FUNCTION: This protein mediates the voltage-dependent sodium ion CC permeability of excitable membranes. Assuming opened or closed CC conformations in response to the voltage difference across the CC membrane, the protein forms a sodium-selective channel through which CC Na(+) ions may pass in accordance with their electrochemical gradient CC (PubMed:1309946, PubMed:21447824, PubMed:25370050, PubMed:23420830, CC PubMed:23085483, PubMed:26279430, PubMed:26392562, PubMed:26776555). It CC is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). CC This channel is responsible for the initial upstroke of the action CC potential. Channel inactivation is regulated by intracellular calcium CC levels (PubMed:19074138). {ECO:0000269|PubMed:1309946, CC ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, CC ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, CC ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, CC ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, CC ECO:0000269|PubMed:26776555}. CC -!- SUBUNIT: Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 CC and SNTB2 (By similarity). Interacts with NEDD4, NEDD4L, WWP2 and GPD1L CC (PubMed:15217910, PubMed:15548568, PubMed:19666841). Interacts with CC CALM (PubMed:21167176, PubMed:22705208, PubMed:25370050). Interacts CC with FGF13; the interaction is direct and FGF13 may regulate SNC5A CC density at membranes and function (PubMed:21817159, PubMed:22705208, CC PubMed:26392562). May also interact with FGF12 and FGF14 CC (PubMed:26392562). Interacts with TMEM233 (PubMed:37117223). Interacts CC with the spider Jingzhaotoxin-I (AC P83974, AC B1P1B7, AC B1P1B8) CC (PubMed:26721415). Interacts with ANK3 (PubMed:15579534). Interacts CC with PKP2 (via N-terminus) (By similarity). CC {ECO:0000250|UniProtKB:P15389, ECO:0000250|UniProtKB:Q9JJV9, CC ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15548568, CC ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:19666841, CC ECO:0000269|PubMed:21167176, ECO:0000269|PubMed:21817159, CC ECO:0000269|PubMed:22705208, ECO:0000269|PubMed:25370050, CC ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26721415, CC ECO:0000305|PubMed:37117223}. CC -!- INTERACTION: CC Q14524; P62158: CALM3; NbExp=14; IntAct=EBI-726858, EBI-397435; CC Q14524; Q13557: CAMK2D; NbExp=16; IntAct=EBI-726858, EBI-351018; CC Q14524; P61328-2: FGF12; NbExp=4; IntAct=EBI-726858, EBI-10699759; CC Q14524; P26045: PTPN3; NbExp=2; IntAct=EBI-726858, EBI-1047946; CC Q14524-3; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-14276801, EBI-11954519; CC Q14524-3; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-14276801, EBI-11524452; CC Q14524-3; Q9Y3B6: EMC9; NbExp=3; IntAct=EBI-14276801, EBI-748366; CC Q14524-3; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-14276801, EBI-750487; CC Q14524-3; Q96E35: ZMYND19; NbExp=4; IntAct=EBI-14276801, EBI-746595; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1309946, CC ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, CC ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, CC ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Cytoplasm, perinuclear CC region {ECO:0000269|PubMed:21447824}. Cell membrane, sarcolemma, T- CC tubule {ECO:0000250|UniProtKB:P15389}. Cell junction CC {ECO:0000250|UniProtKB:P15389}. Note=RANGRF promotes trafficking to the CC cell membrane. Colocalizes with PKP2 at intercalated disks in the heart CC (By similarity). {ECO:0000250|UniProtKB:P15389, CC ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23420830}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=CAG-inclusive variant, Nav1.5c; CC IsoId=Q14524-1; Sequence=Displayed; CC Name=2; Synonyms=Nav1.5b; CC IsoId=Q14524-2; Sequence=VSP_037478; CC Name=3; CC IsoId=Q14524-3; Sequence=VSP_037477, VSP_037478, VSP_037481; CC Name=4; Synonyms=Nav1.5e, neonatal; CC IsoId=Q14524-4; Sequence=VSP_037477; CC Name=5; Synonyms=Ex18del, Nav1.5a; CC IsoId=Q14524-5; Sequence=VSP_037477, VSP_037479; CC Name=6; Synonyms=Ex24del, Nav1.5f; CC IsoId=Q14524-6; Sequence=VSP_037477, VSP_037480; CC -!- TISSUE SPECIFICITY: Found in jejunal circular smooth muscle cells (at CC protein level). Expressed in human atrial and ventricular cardiac CC muscle but not in adult skeletal muscle, brain, myometrium, liver, or CC spleen. Isoform 4 is expressed in brain. {ECO:0000269|PubMed:12358675}. CC -!- DOMAIN: The sequence contains 4 internal repeats, each with 5 CC hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged CC segment (S4). Segments S4 are probably the voltage-sensors and are CC characterized by a series of positively charged amino acids at every CC third position. {ECO:0000305}. CC -!- DOMAIN: The IQ domain mediates association with calmodulin. CC {ECO:0000269|PubMed:21167176, ECO:0000269|PubMed:22705208}. CC -!- PTM: Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not CC seem to be ubiquitinated by NEDD4 or WWP2. CC {ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15548568}. CC -!- PTM: Phosphorylation at Ser-1503 by PKC in a highly conserved CC cytoplasmic loop slows inactivation of the sodium channel and reduces CC peak sodium currents (Probable). Regulated through phosphorylation by CC CaMK2D (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, CC ECO:0000305|PubMed:19666841}. CC -!- PTM: Lacks the cysteine which covalently binds the conotoxin GVIIJ. CC This cysteine (position 868) is speculated in other sodium channel CC subunits alpha to be implied in covalent binding with the sodium CC channel subunit beta-2 or beta-4. {ECO:0000250|UniProtKB:P15389}. CC -!- DISEASE: Progressive familial heart block 1A (PFHB1A) [MIM:113900]: A CC cardiac bundle branch disorder characterized by progressive alteration CC of cardiac conduction through the His-Purkinje system, with a pattern CC of a right bundle-branch block and/or left anterior hemiblock occurring CC individually or together. It leads to complete atrio-ventricular block CC causing syncope and sudden death. {ECO:0000269|PubMed:11234013, CC ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, CC ECO:0000269|PubMed:12574143, ECO:0000269|PubMed:19251209, CC ECO:0000269|PubMed:23420830}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Long QT syndrome 3 (LQT3) [MIM:603830]: A heart disorder CC characterized by a prolonged QT interval on the ECG and polymorphic CC ventricular arrhythmias. They cause syncope and sudden death in CC response to exercise or emotional stress, and can present with a CC sentinel event of sudden cardiac death in infancy. CC {ECO:0000269|PubMed:10377081, ECO:0000269|PubMed:10508990, CC ECO:0000269|PubMed:10590249, ECO:0000269|PubMed:10627139, CC ECO:0000269|PubMed:10911008, ECO:0000269|PubMed:10973849, CC ECO:0000269|PubMed:11304498, ECO:0000269|PubMed:11410597, CC ECO:0000269|PubMed:11710892, ECO:0000269|PubMed:11889015, CC ECO:0000269|PubMed:11997281, ECO:0000269|PubMed:12209021, CC ECO:0000269|PubMed:12454206, ECO:0000269|PubMed:12673799, CC ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16414944, CC ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18060054, CC ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:18451998, CC ECO:0000269|PubMed:18708744, ECO:0000269|PubMed:18848812, CC ECO:0000269|PubMed:18929331, ECO:0000269|PubMed:19716085, CC ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:7651517, CC ECO:0000269|PubMed:7889574, ECO:0000269|PubMed:8541846, CC ECO:0000269|PubMed:9506831, ECO:0000269|PubMed:9686753, CC ECO:0000269|Ref.36}. Note=The disease is caused by variants affecting CC the gene represented in this entry. CC -!- DISEASE: Brugada syndrome 1 (BRGDA1) [MIM:601144]: A tachyarrhythmia CC characterized by right bundle branch block and ST segment elevation on CC an electrocardiogram (ECG). It can cause the ventricles to beat so fast CC that the blood is prevented from circulating efficiently in the body. CC When this situation occurs, the individual will faint and may die in a CC few minutes if the heart is not reset. {ECO:0000269|PubMed:10532948, CC ECO:0000269|PubMed:10618304, ECO:0000269|PubMed:10690282, CC ECO:0000269|PubMed:11410597, ECO:0000269|PubMed:11748104, CC ECO:0000269|PubMed:11823453, ECO:0000269|PubMed:11901046, CC ECO:0000269|PubMed:12051963, ECO:0000269|PubMed:12106943, CC ECO:0000269|PubMed:15023552, ECO:0000269|PubMed:15338453, CC ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:15851320, CC ECO:0000269|PubMed:16266370, ECO:0000269|PubMed:16325048, CC ECO:0000269|PubMed:16616735, ECO:0000269|PubMed:17075016, CC ECO:0000269|PubMed:17081365, ECO:0000269|PubMed:17198989, CC ECO:0000269|PubMed:18252757, ECO:0000269|PubMed:18341814, CC ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:18456723, CC ECO:0000269|PubMed:18616619, ECO:0000269|PubMed:19251209, CC ECO:0000269|PubMed:19272188, ECO:0000269|PubMed:20129283, CC ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, CC ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:26279430, CC ECO:0000269|PubMed:26776555, ECO:0000269|PubMed:32850980, CC ECO:0000269|PubMed:9521325}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Sick sinus syndrome 1 (SSS1) [MIM:608567]: The term 'sick CC sinus syndrome' encompasses a variety of conditions caused by sinus CC node dysfunction. The most common clinical manifestations are syncope, CC presyncope, dizziness, and fatigue. Electrocardiogram typically shows CC sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of CC atrial tachycardias coexisting with sinus bradycardia ('tachycardia- CC bradycardia syndrome') are also common in this disorder. SSS occurs CC most often in the elderly associated with underlying heart disease or CC previous cardiac surgery, but can also occur in the fetus, infant, or CC child without heart disease or other contributing factors. SSS1 onset CC is in utero, infancy, or early childhood. {ECO:0000269|PubMed:11748104, CC ECO:0000269|PubMed:14523039, ECO:0000269|PubMed:22795782}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Familial paroxysmal ventricular fibrillation 1 (VF1) CC [MIM:603829]: A cardiac arrhythmia marked by fibrillary contractions of CC the ventricular muscle due to rapid repetitive excitation of myocardial CC fibers without coordinated contraction of the ventricle and by absence CC of atrial activity. {ECO:0000269|PubMed:10940383}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the CC sudden death of an infant younger than 1 year that remains unexplained CC after a thorough case investigation, including performance of a CC complete autopsy, examination of the death scene, and review of CC clinical history. Pathophysiologic mechanisms for SIDS may include CC respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory CC instability, and inborn errors of metabolism, but definitive pathogenic CC mechanisms precipitating an infant sudden death remain elusive. CC {ECO:0000269|PubMed:18596570, ECO:0000269|PubMed:19302788}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Atrial standstill 1 (ATRST1) [MIM:108770]: A rare arrhythmia CC characterized by the absence of electrical and mechanical activity in CC the atria. Electrocardiographically, it is characterized by CC bradycardia, the absence of P waves, and a junctional narrow complex CC escape rhythm. {ECO:0000269|PubMed:12522116, CC ECO:0000269|PubMed:23420830}. Note=The disease may be caused by CC variants affecting distinct genetic loci, including the gene CC represented in this entry. A mutation in SCN5A has been detected in CC combination with a rare GJA5 genotype in a large family with atrial CC standstill. CC -!- DISEASE: Cardiomyopathy, dilated, 1E (CMD1E) [MIM:601154]: A disorder CC characterized by ventricular dilation and impaired systolic function, CC resulting in congestive heart failure and arrhythmia. Patients are at CC risk of premature death. {ECO:0000269|PubMed:15466643, CC ECO:0000269|PubMed:23420830}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Atrial fibrillation, familial, 10 (ATFB10) [MIM:614022]: A CC familial form of atrial fibrillation, a common sustained cardiac rhythm CC disturbance. Atrial fibrillation is characterized by disorganized CC atrial electrical activity and ineffective atrial contraction promoting CC blood stasis in the atria and reduces ventricular filling. It can CC result in palpitations, syncope, thromboembolic stroke, and congestive CC heart failure. {ECO:0000269|PubMed:18088563, CC ECO:0000269|PubMed:18378609}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Na(+) channels in mammalian cardiac membrane have CC functional properties quite distinct from Na(+) channels in nerve and CC skeletal muscle. CC -!- MISCELLANEOUS: [Isoform 1]: Most abundant isoform in heart. CC -!- MISCELLANEOUS: [Isoform 2]: Very abundant isoform. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Abundantly expressed in neonatal brain and CC heart, slower kinetics of activation and inactivation. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Only detected in neuroblastoma in humans. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: High expression in brain where it accounts CC for nearly 50% of the total transcripts. Non-functional channel, may CC exist to limit the number of undesired functional Nav1.5 channels. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. CC Nav1.5/SCN5A subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M77235; AAA58644.1; -; mRNA. DR EMBL; AY038064; AAK74065.1; -; mRNA. DR EMBL; AY148488; AAN61120.1; -; mRNA. DR EMBL; AF482988; AAO91669.1; -; mRNA. DR EMBL; AB158469; BAD12084.1; -; mRNA. DR EMBL; AB158470; BAD12085.1; -; mRNA. DR EMBL; EF629346; ABR15763.1; -; mRNA. DR EMBL; EF629347; ABR15764.1; -; mRNA. DR EMBL; DQ784809; ABQ01244.1; -; Genomic_DNA. DR EMBL; EF179185; ABN05288.1; -; Genomic_DNA. DR EMBL; AP006241; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC140813; AAI40814.1; -; mRNA. DR EMBL; BC144621; AAI44622.1; -; mRNA. DR EMBL; AB208866; BAD92103.1; -; mRNA. DR CCDS; CCDS46796.1; -. [Q14524-1] DR CCDS; CCDS46797.1; -. [Q14524-2] DR CCDS; CCDS46798.1; -. [Q14524-6] DR CCDS; CCDS46799.1; -. [Q14524-4] DR CCDS; CCDS54569.1; -. [Q14524-5] DR CCDS; CCDS54570.1; -. [Q14524-3] DR PIR; A38195; A38195. DR RefSeq; NP_000326.2; NM_000335.4. [Q14524-2] DR RefSeq; NP_001092874.1; NM_001099404.1. DR RefSeq; NP_001092875.1; NM_001099405.1. DR RefSeq; NP_001153632.1; NM_001160160.1. DR RefSeq; NP_001153633.1; NM_001160161.1. DR RefSeq; NP_932173.1; NM_198056.2. [Q14524-1] DR PDB; 2KBI; NMR; -; A=1773-1865. DR PDB; 2L53; NMR; -; B=1901-1927. DR PDB; 4DCK; X-ray; 2.20 A; A=1773-1940. DR PDB; 4DJC; X-ray; 1.35 A; B=1491-1522. DR PDB; 4JQ0; X-ray; 3.84 A; D=1773-1940. DR PDB; 4OVN; X-ray; 2.80 A; F/G/H/I/J=1773-1929. DR PDB; 5DBR; X-ray; 2.25 A; C=1483-1529. DR PDB; 6LQA; EM; 3.30 A; B=1-2016. DR PDB; 6MUD; X-ray; 2.69 A; B=1786-1922. DR PDB; 7DTC; EM; 3.30 A; A=1-2016. DR PDB; 7L83; NMR; -; A=1597-1633. DR PDBsum; 2KBI; -. DR PDBsum; 2L53; -. DR PDBsum; 4DCK; -. DR PDBsum; 4DJC; -. DR PDBsum; 4JQ0; -. DR PDBsum; 4OVN; -. DR PDBsum; 5DBR; -. DR PDBsum; 6LQA; -. DR PDBsum; 6MUD; -. DR PDBsum; 7DTC; -. DR PDBsum; 7L83; -. DR AlphaFoldDB; Q14524; -. DR BMRB; Q14524; -. DR EMDB; EMD-0942; -. DR EMDB; EMD-30850; -. DR SMR; Q14524; -. DR BioGRID; 112236; 27. DR CORUM; Q14524; -. DR DIP; DIP-38416N; -. DR DIP; DIP-46144N; -. DR IntAct; Q14524; 23. DR MINT; Q14524; -. DR STRING; 9606.ENSP00000328968; -. DR BindingDB; Q14524; -. DR ChEMBL; CHEMBL1980; -. DR DrugBank; DB01426; Ajmaline. DR DrugBank; DB09088; Amylocaine. DR DrugBank; DB01429; Aprindine. DR DrugBank; DB00868; Benzonatate. DR DrugBank; DB13746; Bioallethrin. DR DrugBank; DB05541; Brivaracetam. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB01161; Chloroprocaine. DR DrugBank; DB00527; Cinchocaine. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB13269; Dichlorobenzyl alcohol. DR DrugBank; DB00280; Disopyramide. DR DrugBank; DB04855; Dronedarone. DR DrugBank; DB01228; Encainide. DR DrugBank; DB00754; Ethotoin. DR DrugBank; DB13961; Fish oil. DR DrugBank; DB01195; Flecainide. DR DrugBank; DB01320; Fosphenytoin. DR DrugBank; DB00473; Hexylcaine. DR DrugBank; DB00192; Indecainide. DR DrugBank; DB11633; Isavuconazole. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00532; Mephenytoin. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB00680; Moricizine. DR DrugBank; DB00776; Oxcarbazepine. DR DrugBank; DB11186; Pentoxyverine. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB09345; Pramocaine. DR DrugBank; DB00750; Prilocaine. DR DrugBank; DB01035; Procainamide. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB01182; Propafenone. DR DrugBank; DB09342; Propoxycaine. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB01346; Quinidine barbiturate. DR DrugBank; DB00243; Ranolazine. DR DrugBank; DB00740; Riluzole. DR DrugBank; DB09085; Tetracaine. DR DrugBank; DB01056; Tocainide. DR DrugBank; DB00273; Topiramate. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB06217; Vernakalant. DR DrugBank; DB00909; Zonisamide. DR DrugCentral; Q14524; -. DR GuidetoPHARMACOLOGY; 582; -. DR TCDB; 1.A.1.10.3; the voltage-gated ion channel (vic) superfamily. DR GlyCosmos; Q14524; 15 sites, 1 glycan. DR GlyGen; Q14524; 15 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q14524; -. DR PhosphoSitePlus; Q14524; -. DR SwissPalm; Q14524; -. DR BioMuta; SCN5A; -. DR DMDM; 215273881; -. DR jPOST; Q14524; -. DR MassIVE; Q14524; -. DR PaxDb; 9606-ENSP00000410257; -. DR PeptideAtlas; Q14524; -. DR ProteomicsDB; 18105; -. DR ProteomicsDB; 60021; -. [Q14524-1] DR ProteomicsDB; 60022; -. [Q14524-2] DR ProteomicsDB; 60023; -. [Q14524-3] DR ProteomicsDB; 60024; -. [Q14524-4] DR ProteomicsDB; 60025; -. [Q14524-5] DR ProteomicsDB; 60026; -. [Q14524-6] DR ABCD; Q14524; 4 sequenced antibodies. DR Antibodypedia; 6411; 364 antibodies from 32 providers. DR DNASU; 6331; -. DR Ensembl; ENST00000327956.7; ENSP00000333674.7; ENSG00000183873.18. [Q14524-2] DR Ensembl; ENST00000333535.9; ENSP00000328968.4; ENSG00000183873.18. [Q14524-1] DR Ensembl; ENST00000423572.7; ENSP00000398266.2; ENSG00000183873.18. [Q14524-2] DR GeneID; 6331; -. DR KEGG; hsa:6331; -. DR MANE-Select; ENST00000423572.7; ENSP00000398266.2; NM_000335.5; NP_000326.2. [Q14524-2] DR UCSC; uc062ihe.1; human. [Q14524-1] DR AGR; HGNC:10593; -. DR CTD; 6331; -. DR DisGeNET; 6331; -. DR GeneCards; SCN5A; -. DR GeneReviews; SCN5A; -. DR HGNC; HGNC:10593; SCN5A. DR HPA; ENSG00000183873; Tissue enriched (heart). DR MalaCards; SCN5A; -. DR MIM; 108770; phenotype. DR MIM; 113900; phenotype. DR MIM; 272120; phenotype. DR MIM; 600163; gene. DR MIM; 601144; phenotype. DR MIM; 601154; phenotype. DR MIM; 603829; phenotype. DR MIM; 603830; phenotype. DR MIM; 608567; phenotype. DR MIM; 614022; phenotype. DR neXtProt; NX_Q14524; -. DR OpenTargets; ENSG00000183873; -. DR Orphanet; 1344; Atrial standstill. DR Orphanet; 130; Brugada syndrome. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR Orphanet; 871; Familial progressive cardiac conduction defect. DR Orphanet; 166282; Familial sick sinus syndrome. DR Orphanet; 228140; Idiopathic ventricular fibrillation, non Brugada type. DR Orphanet; 101016; Romano-Ward syndrome. DR PharmGKB; PA304; -. DR VEuPathDB; HostDB:ENSG00000183873; -. DR eggNOG; KOG2301; Eukaryota. DR GeneTree; ENSGT00940000161691; -. DR InParanoid; Q14524; -. DR OrthoDB; 1110761at2759; -. DR PhylomeDB; Q14524; -. DR PathwayCommons; Q14524; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation. DR SignaLink; Q14524; -. DR SIGNOR; Q14524; -. DR BioGRID-ORCS; 6331; 16 hits in 1157 CRISPR screens. DR ChiTaRS; SCN5A; human. DR EvolutionaryTrace; Q14524; -. DR GeneWiki; Nav1.5; -. DR GenomeRNAi; 6331; -. DR Pharos; Q14524; Tclin. DR PRO; PR:Q14524; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q14524; Protein. DR Bgee; ENSG00000183873; Expressed in apex of heart and 112 other cell types or tissues. DR ExpressionAtlas; Q14524; baseline and differential. DR GO; GO:0005901; C:caveola; IDA:BHF-UCL. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL. DR GO; GO:0016328; C:lateral plasma membrane; TAS:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL. DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL. DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central. DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:BHF-UCL. DR GO; GO:0030018; C:Z disc; IDA:UniProtKB. DR GO; GO:0030506; F:ankyrin binding; IDA:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; IPI:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0017134; F:fibroblast growth factor binding; IPI:BHF-UCL. DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IBA:GO_Central. DR GO; GO:0050998; F:nitric-oxide synthase binding; IPI:BHF-UCL. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL. DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB. DR GO; GO:0086060; F:voltage-gated sodium channel activity involved in AV node cell action potential; IMP:BHF-UCL. DR GO; GO:0086061; F:voltage-gated sodium channel activity involved in bundle of His cell action potential; IMP:BHF-UCL. DR GO; GO:0086006; F:voltage-gated sodium channel activity involved in cardiac muscle cell action potential; IDA:BHF-UCL. DR GO; GO:0086062; F:voltage-gated sodium channel activity involved in Purkinje myocyte action potential; IMP:BHF-UCL. DR GO; GO:0086063; F:voltage-gated sodium channel activity involved in SA node cell action potential; IMP:BHF-UCL. DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:0086016; P:AV node cell action potential; IMP:BHF-UCL. DR GO; GO:0086067; P:AV node cell to bundle of His cell communication; IMP:BHF-UCL. DR GO; GO:0003360; P:brainstem development; ISS:BHF-UCL. DR GO; GO:0086043; P:bundle of His cell action potential; IMP:BHF-UCL. DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL. DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL. DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL. DR GO; GO:0003231; P:cardiac ventricle development; ISS:BHF-UCL. DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB. DR GO; GO:0021549; P:cerebellum development; ISS:BHF-UCL. DR GO; GO:0051899; P:membrane depolarization; IDA:BHF-UCL. DR GO; GO:0086010; P:membrane depolarization during action potential; IDA:BHF-UCL. DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; IMP:BHF-UCL. DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; IMP:BHF-UCL. DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:0086047; P:membrane depolarization during Purkinje myocyte cell action potential; IMP:BHF-UCL. DR GO; GO:0086046; P:membrane depolarization during SA node cell action potential; IMP:BHF-UCL. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:BHF-UCL. DR GO; GO:0045760; P:positive regulation of action potential; ISS:BHF-UCL. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:BHF-UCL. DR GO; GO:0010765; P:positive regulation of sodium ion transport; IDA:BHF-UCL. DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; IMP:BHF-UCL. DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; IMP:BHF-UCL. DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IMP:BHF-UCL. DR GO; GO:0002027; P:regulation of heart rate; IMP:UniProtKB. DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL. DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; IMP:BHF-UCL. DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IMP:BHF-UCL. DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:BHF-UCL. DR GO; GO:0086015; P:SA node cell action potential; IMP:BHF-UCL. DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0006814; P:sodium ion transport; IDA:UniProtKB. DR GO; GO:0021537; P:telencephalon development; ISS:BHF-UCL. DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL. DR CDD; cd13433; Na_channel_gate; 1. DR Gene3D; 1.10.287.70; -; 4. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 1.20.5.1190; iswi atpase; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 4. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR008053; Na_channel_a5su. DR InterPro; IPR001696; Na_channel_asu. DR InterPro; IPR044564; Na_chnl_inactivation_gate. DR InterPro; IPR010526; Na_trans_assoc_dom. DR InterPro; IPR024583; Na_trans_cytopl. DR InterPro; IPR043203; VGCC_Ca_Na. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR10037:SF206; SODIUM CHANNEL PROTEIN TYPE 5 SUBUNIT ALPHA; 1. DR PANTHER; PTHR10037; VOLTAGE-GATED CATION CHANNEL CALCIUM AND SODIUM; 1. DR Pfam; PF00520; Ion_trans; 4. DR Pfam; PF06512; Na_trans_assoc; 1. DR Pfam; PF11933; Na_trans_cytopl; 1. DR PRINTS; PR00170; NACHANNEL. DR PRINTS; PR01666; NACHANNEL5. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR Genevisible; Q14524; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Atrial fibrillation; Brugada syndrome; KW Calmodulin-binding; Cardiomyopathy; Cell junction; Cell membrane; KW Cytoplasm; Disease variant; Disulfide bond; Glycoprotein; Ion channel; KW Ion transport; Long QT syndrome; Membrane; Methylation; Phosphoprotein; KW Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation; KW Voltage-gated channel. FT CHAIN 1..2016 FT /note="Sodium channel protein type 5 subunit alpha" FT /id="PRO_0000048497" FT TOPO_DOM 1..131 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 132..150 FT /note="Helical; Name=S1 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 151..157 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 158..178 FT /note="Helical; Name=S2 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 179..192 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 193..210 FT /note="Helical; Name=S3 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 211..216 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 217..233 FT /note="Helical; Name=S4 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 234..252 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 253..272 FT /note="Helical; Name=S5 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 273..357 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 358..382 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 383..389 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 390..410 FT /note="Helical; Name=S6 of repeat I" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 411..717 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 718..736 FT /note="Helical; Name=S1 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 737..747 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 748..767 FT /note="Helical; Name=S2 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 768..781 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 782..801 FT /note="Helical; Name=S3 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 802..803 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 804..821 FT /note="Helical; Name=S4 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 822..837 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 838..856 FT /note="Helical; Name=S5 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 857..883 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 884..904 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 905..917 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 918..938 FT /note="Helical; Name=S6 of repeat II" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 939..1206 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1207..1224 FT /note="Helical; Name=S1 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1225..1237 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1238..1256 FT /note="Helical; Name=S2 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1257..1270 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1271..1289 FT /note="Helical; Name=S3 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1290..1297 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1298..1316 FT /note="Helical; Name=S4 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1317..1333 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1334..1353 FT /note="Helical; Name=S5 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1354..1405 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 1406..1427 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1428..1444 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1445..1466 FT /note="Helical; Name=S6 of repeat III" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1467..1529 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1530..1547 FT /note="Helical; Name=S1 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1548..1558 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1559..1577 FT /note="Helical; Name=S2 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1578..1589 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1590..1607 FT /note="Helical; Name=S3 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1608..1620 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1621..1637 FT /note="Helical; Name=S4 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1638..1656 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 1657..1674 FT /note="Helical; Name=S5 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1675..1696 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 1697..1719 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1720..1748 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 1749..1771 FT /note="Helical; Name=S6 of repeat IV" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1772..2016 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REPEAT 113..420 FT /note="I" FT /evidence="ECO:0000305" FT REPEAT 699..969 FT /note="II" FT /evidence="ECO:0000305" FT REPEAT 1187..1501 FT /note="III" FT /evidence="ECO:0000305" FT REPEAT 1510..1807 FT /note="IV" FT /evidence="ECO:0000305" FT DOMAIN 1901..1930 FT /note="IQ" FT REGION 28..56 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 461..591 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1005..1141 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1839..1901 FT /note="Interaction with FGF13" FT /evidence="ECO:0000269|PubMed:22705208" FT REGION 1959..2016 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1974..1977 FT /note="Interaction with NEDD4, NEDD4L and WWP2" FT /evidence="ECO:0000269|PubMed:15548568" FT COMPBIAS 480..503 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 511..526 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1054..1068 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1090..1118 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1959..1994 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 36 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 38 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 457 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 460 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 483 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 484 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 486 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P15389" FT MOD_RES 497 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 510 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 513 FT /note="Dimethylated arginine; alternate" FT /evidence="ECO:0000269|PubMed:21726068" FT MOD_RES 513 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000269|PubMed:21726068" FT MOD_RES 526 FT /note="Dimethylated arginine; alternate" FT /evidence="ECO:0000269|PubMed:21726068" FT MOD_RES 526 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000269|PubMed:21726068" FT MOD_RES 539 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JJV9" FT MOD_RES 571 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 664 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 667 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23092124" FT MOD_RES 680 FT /note="Dimethylated arginine; alternate" FT /evidence="ECO:0000269|PubMed:21726068" FT MOD_RES 680 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000269|PubMed:21726068" FT MOD_RES 1503 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000305|PubMed:19666841" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 283 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 288 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 291 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 318 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 328 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 740 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 803 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 864 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1365 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1374 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1380 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1388 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1736 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 280..335 FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT DISULFID 906..915 FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT VAR_SEQ 206..211 FT /note="TTEFVD -> VSENIK (in isoform 3, isoform 4, isoform 5 FT and isoform 6)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16115203, ECO:0000303|Ref.6" FT /id="VSP_037477" FT VAR_SEQ 1076 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:12358675, FT ECO:0000303|PubMed:12454206, ECO:0000303|PubMed:14500339, FT ECO:0000303|PubMed:15489334" FT /id="VSP_037478" FT VAR_SEQ 1077..1130 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:16115203" FT /id="VSP_037479" FT VAR_SEQ 1416..1433 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_037480" FT VAR_SEQ 1573..1604 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_037481" FT VARIANT 9 FT /note="G -> V (in LQT3; dbSNP:rs199473043)" FT /evidence="ECO:0000269|PubMed:16922724" FT /id="VAR_036660" FT VARIANT 18 FT /note="R -> Q (in BRGDA1 and LQT3; uncertain significance; FT dbSNP:rs41311087)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074312" FT VARIANT 18 FT /note="R -> W (rare variant; found in a patient with long FT QT syndrome; uncertain significance; dbSNP:rs199473044)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:20129283" FT /id="VAR_068325" FT VARIANT 27 FT /note="R -> H (in BRGDA1 and LQT3; dbSNP:rs199473045)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:19716085" FT /id="VAR_026341" FT VARIANT 30 FT /note="E -> G (in LQT3; uncertain significance; FT dbSNP:rs199473551)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074695" FT VARIANT 34 FT /note="R -> C (in dbSNP:rs6791924)" FT /evidence="ECO:0000269|PubMed:11997281, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283" FT /id="VAR_026342" FT VARIANT 34 FT /note="R -> H (in dbSNP:rs199473046)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074313" FT VARIANT 43 FT /note="R -> Q (in LQT3; does not affect baseline kinetics FT of sodium currents; causes an unusual hyperpolarizing shift FT of the activation kinetics after lidocaine treatment; FT dbSNP:rs199473047)" FT /evidence="ECO:0000269|PubMed:18848812, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055159" FT VARIANT 48 FT /note="E -> K (in LQT3; uncertain significance; FT dbSNP:rs199473048)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074696" FT VARIANT 52 FT /note="P -> S (in LQT3; uncertain significance; FT dbSNP:rs199473553)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074697" FT VARIANT 53 FT /note="R -> Q (in LQT3; uncertain significance; FT dbSNP:rs199473049)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074698" FT VARIANT 70 FT /note="N -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473050)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074314" FT VARIANT 84 FT /note="D -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473051)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074315" FT VARIANT 93 FT /note="F -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473052)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074316" FT VARIANT 94 FT /note="I -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473053)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074317" FT VARIANT 95 FT /note="V -> I (in BRGDA1; dbSNP:rs199473054)" FT /evidence="ECO:0000269|PubMed:17081365" FT /id="VAR_055160" FT VARIANT 104 FT /note="R -> G (in LQT3; uncertain significance; FT dbSNP:rs199473055)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074699" FT VARIANT 104 FT /note="R -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473554)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074318" FT VARIANT 104 FT /note="R -> W (in BRGDA1; uncertain significance; FT dbSNP:rs199473055)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074319" FT VARIANT 109 FT /note="N -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473056)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074320" FT VARIANT 115 FT /note="S -> G (in LQT3; uncertain significance; FT dbSNP:rs199473057)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074700" FT VARIANT 121 FT /note="R -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473058)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074321" FT VARIANT 121 FT /note="R -> W (in BRGDA1; uncertain significance; FT dbSNP:rs199473556)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074322" FT VARIANT 125 FT /note="V -> L (in LQT3; dbSNP:rs199473059)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_068326" FT VARIANT 126 FT /note="K -> E (in BRGDA1; dbSNP:rs185492581)" FT /evidence="ECO:0000269|PubMed:12051963, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026343" FT VARIANT 136 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473557)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074323" FT VARIANT 138 FT /note="M -> I (in ATFB10; dbSNP:rs199473060)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055161" FT VARIANT 146 FT /note="V -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473061)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074324" FT VARIANT 161 FT /note="E -> K (in BRGDA1 and PFHB1A; dbSNP:rs199473062)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_026344" FT VARIANT 161 FT /note="E -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473062)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074325" FT VARIANT 175 FT /note="K -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473063)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074326" FT VARIANT 178 FT /note="A -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473065)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074327" FT VARIANT 182 FT /note="C -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473066)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074328" FT VARIANT 185 FT /note="A -> V (in BRGDA1; uncertain significance; FT dbSNP:rs199473067)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074329" FT VARIANT 187 FT /note="T -> I (in BRGDA1; loss of function; FT dbSNP:rs199473558)" FT /evidence="ECO:0000269|PubMed:16325048" FT /id="VAR_026345" FT VARIANT 204 FT /note="A -> V (in BRGDA1; uncertain significance; FT dbSNP:rs199473559)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074330" FT VARIANT 212 FT /note="L -> P (in LQT3; dbSNP:rs199473070)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_055162" FT VARIANT 212 FT /note="L -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473070)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074331" FT VARIANT 216 FT /note="S -> L (in ATFB10 and BRGDA1; uncertain FT significance; dbSNP:rs41276525)" FT /evidence="ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055163" FT VARIANT 220 FT /note="T -> I (in SSS1 and BRGDA1; dbSNP:rs45620037)" FT /evidence="ECO:0000269|PubMed:14523039, FT ECO:0000269|PubMed:20129283" FT /id="VAR_017670" FT VARIANT 222 FT /note="R -> Q (in BRGDA1 and LQT3; dbSNP:rs45546039)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074332" FT VARIANT 223 FT /note="V -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473560)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074333" FT VARIANT 225 FT /note="R -> Q (in LQT3; dbSNP:rs199473071)" FT /evidence="ECO:0000269|PubMed:16922724" FT /id="VAR_036661" FT VARIANT 225 FT /note="R -> W (in PFHB1A, BRGDA1 and LQT3; FT dbSNP:rs199473072)" FT /evidence="ECO:0000269|PubMed:12574143, FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283" FT /id="VAR_055164" FT VARIANT 226 FT /note="A -> V (in BRGDA1; dbSNP:rs199473561)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026346" FT VARIANT 230 FT /note="I -> V (in BRGDA1; dbSNP:rs199473074)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026347" FT VARIANT 232 FT /note="V -> I (in BRGDA1; uncertain significance; FT dbSNP:rs45471994)" FT /evidence="ECO:0000269|PubMed:18599870, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055165" FT VARIANT 240 FT /note="V -> M (in BRGDA1 and LQT3; dbSNP:rs199473076)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074334" FT VARIANT 245 FT /note="Q -> K (in LQT3; dbSNP:rs199473077)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068327" FT VARIANT 247 FT /note="V -> L (in LQT3; uncertain significance; FT dbSNP:rs199473078)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074701" FT VARIANT 270 FT /note="Q -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473079)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074335" FT VARIANT 275 FT /note="N -> K (in LQT3; uncertain significance; FT dbSNP:rs199473080)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074702" FT VARIANT 276 FT /note="L -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473081)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074336" FT VARIANT 278 FT /note="H -> D (in BRGDA1; uncertain significance; FT dbSNP:rs199473562)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074337" FT VARIANT 282 FT /note="R -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473082)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074338" FT VARIANT 282 FT /note="R -> H (in BRGDA1; dbSNP:rs199473083)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026348" FT VARIANT 286 FT /note="A -> S (in dbSNP:rs61746118)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074339" FT VARIANT 289 FT /note="G -> S (in LQT3; uncertain significance; FT dbSNP:rs199473084)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074703" FT VARIANT 291 FT /note="N -> S (in dbSNP:rs199473563)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074340" FT VARIANT 294 FT /note="V -> M (in BRGDA1; dbSNP:rs199473086)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026349" FT VARIANT 298 FT /note="G -> S (in PFHB1A; also in irritable bowel syndrome; FT results in reduction of whole cell current density and a FT delay in channel activation kinetics without a change in FT single-channel conductance; dbSNP:rs137854608)" FT /evidence="ECO:0000269|PubMed:11804990, FT ECO:0000269|PubMed:19056759" FT /id="VAR_017671" FT VARIANT 299 FT /note="L -> M (in dbSNP:rs199473087)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074341" FT VARIANT 300 FT /note="V -> I (in BRGDA1; uncertain significance; FT dbSNP:rs199473088)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074342" FT VARIANT 315 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473564)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074343" FT VARIANT 319 FT /note="G -> S (in BRGDA1; dbSNP:rs199473090)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026350" FT VARIANT 320 FT /note="T -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473091)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074344" FT VARIANT 325 FT /note="L -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473092)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_055166" FT VARIANT 336 FT /note="P -> L (in BRGDA1; severe reduction of sodium FT currents; dbSNP:rs199473093)" FT /evidence="ECO:0000269|PubMed:17075016, FT ECO:0000269|PubMed:20129283, ECO:0000269|Ref.6" FT /id="VAR_055167" FT VARIANT 340 FT /note="R -> W (in LQT3; uncertain significance; FT dbSNP:rs199473094)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074704" FT VARIANT 351 FT /note="G -> D (in BRGDA1; uncertain significance; FT dbSNP:rs199473095)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074345" FT VARIANT 351 FT /note="G -> V (in BRGDA1; 7-fold current reduction; FT dbSNP:rs199473095)" FT /evidence="ECO:0000269|PubMed:12051963, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026351" FT VARIANT 353 FT /note="T -> I (in BRGDA1; dbSNP:rs199473096)" FT /evidence="ECO:0000269|PubMed:17198989" FT /id="VAR_055168" FT VARIANT 356 FT /note="D -> N (in BRGDA1; loss of function; FT dbSNP:rs199473565)" FT /evidence="ECO:0000269|PubMed:16325048, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026352" FT VARIANT 367 FT /note="R -> C (in BRGDA1 and LQT3; express no current; FT dbSNP:rs199473097)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026353" FT VARIANT 367 FT /note="R -> H (in BRGDA1; express no current; FT dbSNP:rs28937318)" FT /evidence="ECO:0000269|PubMed:11823453, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_017672" FT VARIANT 367 FT /note="R -> L (in BRGDA1; uncertain significance; FT dbSNP:rs28937318)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074346" FT VARIANT 369 FT /note="M -> K (in BRGDA1; dbSNP:rs199473098)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026354" FT VARIANT 370 FT /note="T -> M (in LQT3; uncertain significance; FT dbSNP:rs199473099)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074705" FT VARIANT 374 FT /note="W -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473566)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074347" FT VARIANT 376 FT /note="R -> C (in dbSNP:rs199473100)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074348" FT VARIANT 376 FT /note="R -> H (in BRGDA1 and ATFB10; uncertain FT significance; dbSNP:rs199473101)" FT /evidence="ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055169" FT VARIANT 386 FT /note="G -> E (in BRGDA1; uncertain significance; FT dbSNP:rs199473567)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074349" FT VARIANT 386 FT /note="G -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473102)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074350" FT VARIANT 393 FT /note="Missing (in BRGDA1)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026355" FT VARIANT 396 FT /note="V -> A (in BRGDA1; uncertain significance; FT dbSNP:rs199473103)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074351" FT VARIANT 396 FT /note="V -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473104)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074352" FT VARIANT 397 FT /note="I -> T (in LQT3; uncertain significance; FT dbSNP:rs199473105)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074706" FT VARIANT 404 FT /note="L -> Q (in LQT3; dbSNP:rs199473107)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068328" FT VARIANT 406 FT /note="N -> K (in LQT3; dbSNP:rs199473108)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055170" FT VARIANT 406 FT /note="N -> S (in BRGDA1; dbSNP:rs199473568)" FT /id="VAR_055171" FT VARIANT 409 FT /note="L -> V (in LQT3; uncertain significance; FT dbSNP:rs199473109)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074707" FT VARIANT 411 FT /note="V -> M (in LQT3; dbSNP:rs72549410)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_068329" FT VARIANT 413 FT /note="A -> E (in LQT3; uncertain significance; FT dbSNP:rs199473569)" FT /evidence="ECO:0000269|PubMed:16414944" FT /id="VAR_074708" FT VARIANT 413 FT /note="A -> T (in LQT3; uncertain significance; FT dbSNP:rs199473110)" FT /evidence="ECO:0000269|PubMed:16414944" FT /id="VAR_074709" FT VARIANT 428 FT /note="E -> K (in ATFB10; dbSNP:rs199473111)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055172" FT VARIANT 429 FT /note="Missing (in LQT3; uncertain significance; FT dbSNP:rs761375502)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074710" FT VARIANT 439 FT /note="E -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473570)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074353" FT VARIANT 445 FT /note="H -> D (in ATFB10; dbSNP:rs199473112)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055173" FT VARIANT 447 FT /note="A -> G (in dbSNP:rs199473113)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074354" FT VARIANT 449 FT /note="T -> A (in dbSNP:rs199473571)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074355" FT VARIANT 461 FT /note="L -> V (in dbSNP:rs41313697)" FT /evidence="ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055174" FT VARIANT 462 FT /note="E -> A (in LQT3; uncertain significance; FT dbSNP:rs199473114)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074711" FT VARIANT 462 FT /note="E -> K (in LQT3; dbSNP:rs199473572)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068330" FT VARIANT 470 FT /note="N -> K (in ATFB10; dbSNP:rs199473115)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055175" FT VARIANT 475 FT /note="R -> S (in dbSNP:rs199473116)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074356" FT VARIANT 481 FT /note="R -> W (in dbSNP:rs144511230)" FT /evidence="ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055176" FT VARIANT 501 FT /note="D -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473117)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074357" FT VARIANT 512 FT /note="T -> I (in PFHB1A; voltage-dependent activation and FT inactivation of the I-512 channel is shifted negatively by FT 8 to 9 mV and had enhanced slow activation and slower FT recovery from inactivation commpared to the wild-type FT channel; the double mutant R-558/I-512 channel shows that FT R-558 eliminates the negative shift induced by I-512 but FT only partially restores the kinetic abnormalities; FT dbSNP:rs199473118)" FT /evidence="ECO:0000269|PubMed:12569159" FT /id="VAR_036662" FT VARIANT 514 FT /note="G -> C (in BRGDA1 and PFHB1A; dbSNP:rs137854606)" FT /evidence="ECO:0000269|PubMed:11234013, FT ECO:0000269|PubMed:19251209" FT /id="VAR_017673" FT VARIANT 524 FT /note="S -> Y (in dbSNP:rs41313691)" FT /evidence="ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:20129283" FT /id="VAR_036663" FT VARIANT 526 FT /note="R -> H (in BRGDA1; uncertain significance; FT dbSNP:rs45627438)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074358" FT VARIANT 530 FT /note="F -> V (in LQT3; uncertain significance; FT dbSNP:rs199473120)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074712" FT VARIANT 532 FT /note="F -> C (in SIDS and BRGDA1; dbSNP:rs199473573)" FT /evidence="ECO:0000269|PubMed:18596570, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055177" FT VARIANT 535 FT /note="R -> Q (in LQT3; uncertain significance; FT dbSNP:rs199473121)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074713" FT VARIANT 543 FT /note="F -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473122)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074359" FT VARIANT 552 FT /note="G -> R (in BRGDA1; dbSNP:rs3918389)" FT /evidence="ECO:0000269|PubMed:12358675, FT ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:16616735, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026356" FT VARIANT 558 FT /note="H -> R (channels properties are similar to FT wild-type; the double mutant R-558/I-512 channel shows that FT R-558 eliminates the negative shift induced by Ile-512 but FT only partially restores the kinetic abnormalities; can FT modulate the gating defects caused by Ala-2006 and other FT mutations; dbSNP:rs1805124)" FT /evidence="ECO:0000269|PubMed:11997281, FT ECO:0000269|PubMed:12051963, ECO:0000269|PubMed:12454206, FT ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:14500339, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18368697, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283, FT ECO:0000269|PubMed:21109022, ECO:0000269|PubMed:23085483" FT /id="VAR_008955" FT VARIANT 567 FT /note="L -> Q (in BRGDA1; dbSNP:rs199473124)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026357" FT VARIANT 568 FT /note="R -> H (in dbSNP:rs199473125)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074360" FT VARIANT 569 FT /note="R -> W (in LQT3; uncertain significance; FT dbSNP:rs199473576)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074714" FT VARIANT 571 FT /note="S -> I (in LQT3; uncertain significance; FT dbSNP:rs199473126)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074715" FT VARIANT 572 FT /note="A -> D (in LQT3 and ATFB10; likely benign; FT dbSNP:rs36210423)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:18378609" FT /id="VAR_055178" FT VARIANT 572 FT /note="A -> S (in LQT3; uncertain significance; FT dbSNP:rs184442491)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074716" FT VARIANT 572 FT /note="A -> V (in LQT3; uncertain significance; FT dbSNP:rs36210423)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074717" FT VARIANT 573 FT /note="Q -> E (in LQT3; uncertain significance; FT dbSNP:rs199473127)" FT /evidence="ECO:0000269|PubMed:16414944" FT /id="VAR_074718" FT VARIANT 579 FT /note="G -> R (in LQT3; uncertain significance; FT dbSNP:rs199473128)" FT /evidence="ECO:0000269|PubMed:16414944, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074361" FT VARIANT 586..587 FT /note="Missing (in LQT3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_055179" FT VARIANT 592 FT /note="N -> K (in dbSNP:rs199473130)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074362" FT VARIANT 596 FT /note="D -> G (in dbSNP:rs199473131)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074363" FT VARIANT 601 FT /note="V -> A (in dbSNP:rs199473132)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074364" FT VARIANT 615 FT /note="G -> E (in LQT3 and BRGDA1; drug-induced LQT FT syndrome; dbSNP:rs12720452)" FT /evidence="ECO:0000269|PubMed:11997281, FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026358" FT VARIANT 618 FT /note="L -> F (in dbSNP:rs45488304)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283" FT /id="VAR_047360" FT VARIANT 619 FT /note="L -> F (in LQT3 and BRGDA1; dbSNP:rs199473133)" FT /evidence="ECO:0000269|PubMed:11997281, FT ECO:0000269|PubMed:12673799, ECO:0000269|PubMed:20129283" FT /id="VAR_015682" FT VARIANT 620 FT /note="R -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473577)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074365" FT VARIANT 632 FT /note="T -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473134)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074366" FT VARIANT 637 FT /note="P -> L (in LQT3; dbSNP:rs199473135)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068331" FT VARIANT 638 FT /note="G -> D (in dbSNP:rs199473578)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074367" FT VARIANT 639 FT /note="G -> R (in LQT3; dbSNP:rs199473136)" FT /evidence="ECO:0000269|PubMed:16922724, FT ECO:0000269|PubMed:19716085" FT /id="VAR_036664" FT VARIANT 640 FT /note="P -> A (in BRGDA1; uncertain significance; FT dbSNP:rs199473137)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074368" FT VARIANT 647 FT /note="A -> D (in BRGDA1; uncertain significance; FT dbSNP:rs185638763)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074369" FT VARIANT 648 FT /note="P -> L (in LQT3 and BRGDA1; dbSNP:rs45609733)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:20129283" FT /id="VAR_068332" FT VARIANT 654 FT /note="E -> K (in LQT3; uncertain significance; FT dbSNP:rs199473138)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074719" FT VARIANT 655 FT /note="E -> K (in ATFB10; dbSNP:rs199473579)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055180" FT VARIANT 656 FT /note="P -> L (in dbSNP:rs41313681)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074370" FT VARIANT 661 FT /note="R -> W (in BRGDA1; uncertain significance; FT dbSNP:rs199473139)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074371" FT VARIANT 672 FT /note="A -> T (in dbSNP:rs199473140)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074372" FT VARIANT 673 FT /note="L -> P (in LQT3; uncertain significance; FT dbSNP:rs199473141)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074720" FT VARIANT 680 FT /note="R -> H (in LQT3; dbSNP:rs199473142)" FT /id="VAR_055181" FT VARIANT 681 FT /note="H -> P (in BRGDA1; dbSNP:rs199473143)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026359" FT VARIANT 683 FT /note="C -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473144)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074373" FT VARIANT 689 FT /note="R -> C (in LQT3; uncertain significance; FT dbSNP:rs199473580)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074721" FT VARIANT 689 FT /note="R -> H (in LQT3; uncertain significance; FT dbSNP:rs199473145)" FT /evidence="ECO:0000269|PubMed:16414944, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074374" FT VARIANT 692 FT /note="Q -> K (in dbSNP:rs45553235)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074375" FT VARIANT 701 FT /note="P -> L (in BRGDA1 and LQT3; dbSNP:rs199473147)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074376" FT VARIANT 705 FT /note="S -> F (in dbSNP:rs199473148)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074377" FT VARIANT 717 FT /note="P -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473149)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074378" FT VARIANT 731 FT /note="T -> I (in LQT3; uncertain significance; FT dbSNP:rs199473150)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074722" FT VARIANT 735 FT /note="A -> E (in BRGDA1; dbSNP:rs137854611)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026360" FT VARIANT 735 FT /note="A -> V (in BRGDA1 and SSS1; expresses currents with FT steady state activation voltage shifted to more positive FT potentials and exhibit reduced sodium channel current at FT the end of phase I of the action potential; FT dbSNP:rs137854611)" FT /evidence="ECO:0000269|PubMed:11823453, FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:22795782" FT /id="VAR_017674" FT VARIANT 746 FT /note="E -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473582)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074379" FT VARIANT 750 FT /note="Q -> R (in LQT3; uncertain significance; FT dbSNP:rs199473152)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074723" FT VARIANT 752 FT /note="G -> R (in BRGDA1 and PFHB1A; dbSNP:rs199473153)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_026361" FT VARIANT 758 FT /note="G -> E (in BRGDA1; uncertain significance; FT dbSNP:rs199473154)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074380" FT VARIANT 764 FT /note="M -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473156)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074381" FT VARIANT 772 FT /note="D -> N (in BRGDA1 and LQT3; dbSNP:rs199473157)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074382" FT VARIANT 773 FT /note="P -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473158)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074383" FT VARIANT 789 FT /note="V -> I (in BRGDA1; uncertain significance; FT dbSNP:rs199473159)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074384" FT VARIANT 808 FT /note="R -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473160)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074385" FT VARIANT 812 FT /note="L -> Q (in BRGDA1; decreased protein abundance; FT retained intracellularly; decreased voltage-gated sodium FT channel activity; hyperpolarizing shift of the voltage FT dependence of inactivation leading to reduced sodium window FT current; no dominant negative effect)" FT /evidence="ECO:0000269|PubMed:26279430" FT /id="VAR_076555" FT VARIANT 814 FT /note="R -> Q (in BRGDA1; dbSNP:rs199473584)" FT /id="VAR_055182" FT VARIANT 816 FT /note="F -> Y (in LQT3; uncertain significance; FT dbSNP:rs199473162)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074724" FT VARIANT 817 FT /note="K -> E (in BRGDA1; no effect on localization to the FT plasma membrane; decreased voltage-gated sodium channel FT activity; shift in the voltage dependence of activation and FT changed recovery from inactivation)" FT /evidence="ECO:0000269|PubMed:26776555" FT /id="VAR_076556" FT VARIANT 839 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473164)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074386" FT VARIANT 848 FT /note="I -> F (in LQT3; uncertain significance; FT dbSNP:rs199473166)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074725" FT VARIANT 851 FT /note="F -> L (in BRGDA1; dbSNP:rs199473586)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026362" FT VARIANT 867 FT /note="E -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473167)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074387" FT VARIANT 878 FT /note="R -> C (in BRGDA1; dbSNP:rs199473168)" FT /evidence="ECO:0000269|PubMed:18616619, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055183" FT VARIANT 878 FT /note="R -> H (in BRGDA1; uncertain significance; FT dbSNP:rs199473587)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074388" FT VARIANT 886 FT /note="H -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473169)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074389" FT VARIANT 892 FT /note="F -> I (in BRGDA1; dbSNP:rs199473170)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026363" FT VARIANT 893 FT /note="R -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473171)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074390" FT VARIANT 893 FT /note="R -> H (in BRGDA1; uncertain significance; FT dbSNP:rs199473172)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074391" FT VARIANT 896 FT /note="C -> S (in BRGDA1; dbSNP:rs199473173)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026364" FT VARIANT 901 FT /note="E -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473174)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074392" FT VARIANT 910 FT /note="S -> L (in BRGDA1; dbSNP:rs199473175)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026365" FT VARIANT 915 FT /note="C -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473588)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074393" FT VARIANT 917 FT /note="L -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473176)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074394" FT VARIANT 924 FT /note="V -> I (in dbSNP:rs199473177)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074395" FT VARIANT 927 FT /note="N -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473589)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074396" FT VARIANT 928 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473178)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074397" FT VARIANT 935 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473179)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074398" FT VARIANT 941 FT /note="S -> N (in LQT3; also in SIDS; dbSNP:rs137854605)" FT /evidence="ECO:0000269|PubMed:10911008" FT /id="VAR_017675" FT VARIANT 960 FT /note="Q -> K (in LQT3; uncertain significance; FT dbSNP:rs199473590)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074726" FT VARIANT 965 FT /note="R -> C (in BRGDA1; steady state inactivation shifted FT to a more negative potential; slower recovery from FT inactivation; dbSNP:rs199473180)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:19272188, ECO:0000269|PubMed:20129283" FT /id="VAR_026366" FT VARIANT 965 FT /note="R -> H (in BRGDA1; uncertain significance; FT dbSNP:rs199473181)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074399" FT VARIANT 965 FT /note="R -> L (in LQT3; uncertain significance; FT dbSNP:rs199473181)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074727" FT VARIANT 971 FT /note="R -> C (in LQT3; dbSNP:rs61737825)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068333" FT VARIANT 981 FT /note="C -> F (in LQT3; uncertain significance; FT dbSNP:rs199473591)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074728" FT VARIANT 986 FT /note="R -> Q (in dbSNP:rs41313667)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074400" FT VARIANT 997 FT /note="A -> S (in LQT3; also found in patients with atrial FT fibrillation; sodium current characterized by slower decay FT and a 2- to 3-fold increase in late sodium current; FT dbSNP:rs137854609)" FT /evidence="ECO:0000269|PubMed:11710892, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:19716085" FT /id="VAR_017676" FT VARIANT 997 FT /note="A -> T (in BRGDA1; uncertain significance; FT dbSNP:rs137854609)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074401" FT VARIANT 1004 FT /note="C -> R (in LQT3; uncertain significance; FT dbSNP:rs199473183)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074729" FT VARIANT 1016 FT /note="T -> M (in dbSNP:rs199473185)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074402" FT VARIANT 1023 FT /note="R -> H (in BRGDA1; dbSNP:rs199473592)" FT /id="VAR_055184" FT VARIANT 1027 FT /note="R -> Q (in dbSNP:rs763891399)" FT /evidence="ECO:0000269|PubMed:1309946, FT ECO:0000269|PubMed:16616735, ECO:0000269|Ref.6" FT /id="VAR_026367" FT VARIANT 1040 FT /note="G -> R (in dbSNP:rs199473186)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074403" FT VARIANT 1041 FT /note="D -> N (in dbSNP:rs45491996)" FT /id="VAR_047361" FT VARIANT 1053 FT /note="E -> K (in BRGDA1, ATFB10 and LQT3; abolishes FT binding to ANK3 and also prevents accumulation of SCN5A at FT cell surface sites in ventricular cardiomyocytes; FT dbSNP:rs137854617)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283" FT /id="VAR_026368" FT VARIANT 1055 FT /note="D -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473593)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074404" FT VARIANT 1069 FT /note="T -> M (in LQT3; dbSNP:rs199473187)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_068334" FT VARIANT 1079 FT /note="S -> Y (in BRGDA1; uncertain significance; FT dbSNP:rs199473188)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074405" FT VARIANT 1082 FT /note="V -> A (in dbSNP:rs199473189)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074406" FT VARIANT 1084 FT /note="G -> S (in SIDS; uncertain significance; FT dbSNP:rs199473190)" FT /evidence="ECO:0000269|PubMed:18596570" FT /id="VAR_055185" FT VARIANT 1090 FT /note="P -> L (in dbSNP:rs1805125)" FT /evidence="ECO:0000269|PubMed:18368697, FT ECO:0000269|PubMed:20129283" FT /id="VAR_014464" FT VARIANT 1098 FT /note="V -> L (in dbSNP:rs199473191)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074407" FT VARIANT 1100 FT /note="A -> V (in LQT3; uncertain significance; FT dbSNP:rs199473192)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074730" FT VARIANT 1103 FT /note="S -> Y (may confer susceptibility to acquired FT arrhythmia; dbSNP:rs7626962)" FT /evidence="ECO:0000269|PubMed:12193783, FT ECO:0000269|PubMed:12471205, ECO:0000269|PubMed:14500339, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283" FT /id="VAR_017677" FT VARIANT 1107 FT /note="E -> K (in dbSNP:rs199473193)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074408" FT VARIANT 1113 FT /note="A -> V (in BRGDA1; uncertain significance; FT dbSNP:rs199473194)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074409" FT VARIANT 1114 FT /note="D -> N (in LQT3; dbSNP:rs199473195)" FT /evidence="ECO:0000269|PubMed:10973849, FT ECO:0000269|PubMed:19716085" FT /id="VAR_009935" FT VARIANT 1116 FT /note="R -> W (in dbSNP:rs199473196)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074410" FT VARIANT 1131 FT /note="T -> I (in ATFB10; dbSNP:rs199473197)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055186" FT VARIANT 1140 FT /note="S -> T (in BRGDA1; uncertain significance; FT dbSNP:rs199473199)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074411" FT VARIANT 1166 FT /note="D -> N (in LQT3; uncertain significance; FT dbSNP:rs199473594)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074731" FT VARIANT 1180 FT /note="A -> V (in dbSNP:rs41310765)" FT /id="VAR_047362" FT VARIANT 1193 FT /note="R -> Q (in BRGDA1 and LQT3; also found in patients FT with atrial fibrillation; accelerates the inactivation of FT the sodium channel current and exhibit reduced sodium FT channel current at the end of phase I of the action FT potential; dbSNP:rs41261344)" FT /evidence="ECO:0000269|PubMed:11823453, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283" FT /id="VAR_017678" FT VARIANT 1199 FT /note="Y -> S (in LQT3; uncertain significance; FT dbSNP:rs199473202)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074732" FT VARIANT 1212 FT /note="Missing (in LQT3; uncertain significance; FT dbSNP:rs794728920)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074733" FT VARIANT 1219 FT /note="S -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473597)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074412" FT VARIANT 1225 FT /note="E -> K (in BRGDA1 and LQT3; dbSNP:rs199473204)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:20129283" FT /id="VAR_026369" FT VARIANT 1228 FT /note="Y -> H (in BRGDA1; uncertain significance; FT dbSNP:rs199473205)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074413" FT VARIANT 1231 FT /note="E -> K (in LQT3; dbSNP:rs199473598)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068335" FT VARIANT 1232 FT /note="R -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473206)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074414" FT VARIANT 1232 FT /note="R -> W (in BRGDA1 and PFHB1A; dbSNP:rs199473207)" FT /evidence="ECO:0000269|PubMed:19251209, FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:9521325" FT /id="VAR_017679" FT VARIANT 1236 FT /note="K -> N (in BRGDA1; dbSNP:rs199473208)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026370" FT VARIANT 1239 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473210)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074415" FT VARIANT 1240 FT /note="E -> Q (in dbSNP:rs199473211)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026371" FT VARIANT 1243 FT /note="D -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473599)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074416" FT VARIANT 1249 FT /note="V -> D (in BRGDA1; uncertain significance; FT dbSNP:rs199473213)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074417" FT VARIANT 1250 FT /note="F -> L (in LQT3; drug-induced LQT syndrome; FT dbSNP:rs45589741)" FT /evidence="ECO:0000269|PubMed:11997281" FT /id="VAR_026372" FT VARIANT 1251 FT /note="V -> M (in dbSNP:rs199473600)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074418" FT VARIANT 1253 FT /note="E -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473214)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074419" FT VARIANT 1262 FT /note="G -> S (in BRGDA1; uncertain significance; FT dbSNP:rs137854616)" FT /evidence="ECO:0000269|PubMed:15338453, FT ECO:0000269|PubMed:20129283" FT /id="VAR_036665" FT VARIANT 1271 FT /note="W -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473601)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074420" FT VARIANT 1275 FT /note="D -> N (in CMD1E, BRGDA1, PFHB1A and ATRST1; in FT familial atrial standstill is found in association with FT variants in the regulatory region of GJA5; decreases FT expression at the cell membrane; alters channel kinetics; FT shifts activation and inactivation to more positive FT membrane potentials; dbSNP:rs137854618)" FT /evidence="ECO:0000269|PubMed:12522116, FT ECO:0000269|PubMed:15466643, ECO:0000269|PubMed:19251209, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026373" FT VARIANT 1283 FT /note="L -> M (in LQT3; uncertain significance; FT dbSNP:rs199473216)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074734" FT VARIANT 1288 FT /note="A -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473217)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074421" FT VARIANT 1293 FT /note="F -> S (in BRGDA1; uncertain significance; FT dbSNP:rs41311127)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026374" FT VARIANT 1295 FT /note="E -> K (in LQT3; causes significant positive shifts FT in the half-maximal voltage of steady-state inactivation FT and activation; dbSNP:rs199473218)" FT /evidence="ECO:0000269|PubMed:11304498" FT /id="VAR_055187" FT VARIANT 1298 FT /note="P -> L (in SSS1; dbSNP:rs28937319)" FT /evidence="ECO:0000269|PubMed:14523039" FT /id="VAR_017680" FT VARIANT 1304 FT /note="T -> M (in LQT3; dbSNP:rs199473603)" FT /evidence="ECO:0000269|PubMed:10508990, FT ECO:0000269|PubMed:19716085" FT /id="VAR_008956" FT VARIANT 1308 FT /note="L -> F (associated with I-232 in a case of FT lidocaine-induced Brugada syndrome; dbSNP:rs41313031)" FT /evidence="ECO:0000269|PubMed:18599870, FT ECO:0000269|PubMed:20129283" FT /id="VAR_055188" FT VARIANT 1311 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473219)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074422" FT VARIANT 1319 FT /note="G -> V (in BRGDA1; dbSNP:rs199473220)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_026375" FT VARIANT 1323 FT /note="V -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473221)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074423" FT VARIANT 1325 FT /note="N -> S (in LQT3; dbSNP:rs28937317)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_001577" FT VARIANT 1326 FT /note="A -> S (in LQT3; uncertain significance; FT dbSNP:rs199473222)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074735" FT VARIANT 1330 FT /note="A -> P (in LQT3; dbSNP:rs199473224)" FT /id="VAR_055189" FT VARIANT 1330 FT /note="A -> T (in LQT3; dbSNP:rs199473224)" FT /id="VAR_055190" FT VARIANT 1332 FT /note="P -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473225)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_055191" FT VARIANT 1333 FT /note="S -> Y (in LQT3 and SIDS; dbSNP:rs199473604)" FT /evidence="ECO:0000269|PubMed:16922724, FT ECO:0000269|PubMed:19302788" FT /id="VAR_036666" FT VARIANT 1334 FT /note="I -> V (in LQT3; uncertain significance; FT dbSNP:rs199473226)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074736" FT VARIANT 1338 FT /note="L -> V (in LQT3; uncertain significance; FT dbSNP:rs199473227)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074737" FT VARIANT 1344 FT /note="F -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473228)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074424" FT VARIANT 1344 FT /note="F -> S (in BRGDA1; dbSNP:rs199473229)" FT /evidence="ECO:0000269|PubMed:16616735" FT /id="VAR_026376" FT VARIANT 1346 FT /note="L -> I (in BRGDA1; uncertain significance; FT dbSNP:rs199473230)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074425" FT VARIANT 1346 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473231)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074426" FT VARIANT 1351 FT /note="M -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473232)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074427" FT VARIANT 1353 FT /note="V -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473233)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074428" FT VARIANT 1358 FT /note="G -> W (in BRGDA1; uncertain significance; FT dbSNP:rs199473234)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074429" FT VARIANT 1359 FT /note="K -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473235)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074430" FT VARIANT 1360 FT /note="F -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473236)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074431" FT VARIANT 1363 FT /note="C -> Y (in BRGDA1; uncertain significance; FT dbSNP:rs199473237)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074432" FT VARIANT 1382 FT /note="S -> I (in BRGDA1; dbSNP:rs199473608)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026377" FT VARIANT 1405 FT /note="V -> L (in BRGDA1; dbSNP:rs199473239)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026378" FT VARIANT 1405 FT /note="V -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473239)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074433" FT VARIANT 1406 FT /note="G -> E (in BRGDA1; uncertain significance; FT dbSNP:rs199473609)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074434" FT VARIANT 1406 FT /note="G -> R (in BRGDA1; dbSNP:rs199473240)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:20129283" FT /id="VAR_026379" FT VARIANT 1408 FT /note="G -> R (in SSS1 and BRGDA1; dbSNP:rs137854612)" FT /evidence="ECO:0000269|PubMed:11748104, FT ECO:0000269|PubMed:14523039, ECO:0000269|PubMed:19251209, FT ECO:0000269|PubMed:20129283" FT /id="VAR_017681" FT VARIANT 1409 FT /note="Y -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473610)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074435" FT VARIANT 1412 FT /note="L -> F (in BRGDA1; uncertain significance; FT dbSNP:rs199473241)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074436" FT VARIANT 1419 FT /note="K -> E (in BRGDA1; uncertain significance; FT dbSNP:rs199473242)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074437" FT VARIANT 1420 FT /note="G -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473611)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074438" FT VARIANT 1427 FT /note="A -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473244)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074439" FT VARIANT 1428 FT /note="A -> V (in BRGDA1; uncertain significance; FT dbSNP:rs199473612)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074440" FT VARIANT 1432 FT /note="R -> G (in BRGDA1; uncertain significance; FT dbSNP:rs199473245)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_055192" FT VARIANT 1432 FT /note="R -> S (in BRGDA1 and LQT3; dbSNP:rs199473246)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074441" FT VARIANT 1433 FT /note="G -> V (in BRGDA1; uncertain significance; FT dbSNP:rs199473247)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074442" FT VARIANT 1438 FT /note="P -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473248)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_055193" FT VARIANT 1441 FT /note="E -> Q (in BRGDA1; uncertain significance; FT dbSNP:rs199473249)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074443" FT VARIANT 1448 FT /note="I -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473250)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074444" FT VARIANT 1448 FT /note="I -> T (in BRGDA1; uncertain significance; FT dbSNP:rs199473251)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074445" FT VARIANT 1449 FT /note="Y -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473613)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074446" FT VARIANT 1451 FT /note="V -> D (in BRGDA1; uncertain significance; FT dbSNP:rs199473252)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074447" FT VARIANT 1458 FT /note="S -> Y (in LQT3; dbSNP:rs199473253)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068336" FT VARIANT 1463 FT /note="N -> Y (in BRGDA1; uncertain significance; FT dbSNP:rs199473614)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074448" FT VARIANT 1468 FT /note="V -> F (in BRGDA1; uncertain significance; FT dbSNP:rs199473254)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074449" FT VARIANT 1472 FT /note="N -> S (in LQT3; uncertain significance; FT dbSNP:rs199473255)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074738" FT VARIANT 1473 FT /note="F -> C (in LQT3; dbSNP:rs199473256)" FT /evidence="ECO:0000269|PubMed:18060054, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055194" FT VARIANT 1479 FT /note="Missing (in BRGDA1)" FT /evidence="ECO:0000269|PubMed:12106943" FT /id="VAR_026380" FT VARIANT 1481 FT /note="G -> E (in LQT3; dbSNP:rs199473257)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_068337" FT VARIANT 1486 FT /note="F -> L (in LQT3; dbSNP:rs199473615)" FT /id="VAR_055195" FT VARIANT 1487 FT /note="M -> L (in LQT3; uncertain significance; FT dbSNP:rs199473258)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074739" FT VARIANT 1488 FT /note="T -> R (in LQT3; uncertain significance; FT dbSNP:rs199473259)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074740" FT VARIANT 1489 FT /note="E -> D (in LQT3; uncertain significance; FT dbSNP:rs199473616)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074741" FT VARIANT 1493 FT /note="K -> R (in LQT3; uncertain significance; FT dbSNP:rs199473260)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074742" FT VARIANT 1494 FT /note="Y -> N (in BRGDA1; dbSNP:rs199473261)" FT /evidence="ECO:0000269|PubMed:18341814" FT /id="VAR_055196" FT VARIANT 1495 FT /note="Y -> S (in LQT3; uncertain significance; FT dbSNP:rs199473262)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074743" FT VARIANT 1498 FT /note="M -> T (found in a patient with long QT syndrome; FT uncertain significance; dbSNP:rs199473263)" FT /evidence="ECO:0000269|PubMed:16115203, FT ECO:0000269|PubMed:16414944" FT /id="VAR_074744" FT VARIANT 1498 FT /note="M -> V (in LQT3; uncertain significance; FT dbSNP:rs199473264)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074745" FT VARIANT 1500 FT /note="K -> N (in dbSNP:rs199473265)" FT /evidence="ECO:0000269|PubMed:10508990" FT /id="VAR_008957" FT VARIANT 1500 FT /note="Missing (in BRGDA1)" FT /evidence="ECO:0000269|PubMed:11901046" FT /id="VAR_026381" FT VARIANT 1501 FT /note="L -> V (in LQT3 and BRGDA1; dbSNP:rs199473266)" FT /evidence="ECO:0000269|PubMed:10973849, FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283" FT /id="VAR_009936" FT VARIANT 1502 FT /note="G -> S (in BRGDA1; dbSNP:rs199473267)" FT /evidence="ECO:0000269|PubMed:12106943" FT /id="VAR_026382" FT VARIANT 1505..1507 FT /note="Missing (in LQT3)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:7651517" FT /id="VAR_001576" FT VARIANT 1505 FT /note="K -> N (in LQT3; uncertain significance; FT dbSNP:rs199473268)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074746" FT VARIANT 1507..1509 FT /note="Missing (in LQT3)" FT /id="VAR_055197" FT VARIANT 1512 FT /note="R -> W (in BRGDA1; significantly affects cardiac FT sodium channel characteristics; associated with an increase FT in inward sodium current during the action potential FT upstroke; dbSNP:rs137854602)" FT /evidence="ECO:0000269|PubMed:10690282, FT ECO:0000269|PubMed:12106943, ECO:0000269|PubMed:19251209, FT ECO:0000269|PubMed:20129283" FT /id="VAR_017682" FT VARIANT 1521 FT /note="I -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473617)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074450" FT VARIANT 1525 FT /note="V -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473269)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074451" FT VARIANT 1527 FT /note="K -> R (in BRGDA1; asymptomatic patient; associated FT with P-1569; dbSNP:rs199473270)" FT /evidence="ECO:0000269|PubMed:15851320" FT /id="VAR_055198" FT VARIANT 1532 FT /note="V -> I (in LQT3; uncertain significance; FT dbSNP:rs199473618)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074747" FT VARIANT 1548 FT /note="E -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473271)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074452" FT VARIANT 1560 FT /note="L -> F (in LQT3; uncertain significance; FT dbSNP:rs199473619)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074748" FT VARIANT 1569 FT /note="A -> P (in BRGDA1; asymptomatic patient; associated FT with R-1527; dbSNP:rs199473273)" FT /evidence="ECO:0000269|PubMed:15851320" FT /id="VAR_055199" FT VARIANT 1571 FT /note="F -> C (in BRGDA1; uncertain significance; FT dbSNP:rs199473274)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074453" FT VARIANT 1571 FT /note="F -> L (in BRGDA1; affects channel activity; the FT mutant displays a hyperpolarizing shift in the voltage FT dependence of inactivation causing slower inactivation FT compared to the wild type, slower recovery and a reduced FT availability of channels at rest; dbSNP:rs1369632373)" FT /evidence="ECO:0000269|PubMed:32850980" FT /id="VAR_085793" FT VARIANT 1574 FT /note="E -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473620)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074454" FT VARIANT 1582 FT /note="L -> P (in BRGDA1; uncertain significance; FT dbSNP:rs199473275)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074455" FT VARIANT 1583 FT /note="R -> C (in BRGDA1; uncertain significance; FT dbSNP:rs45514691)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074456" FT VARIANT 1583 FT /note="R -> H (in BRGDA1; uncertain significance; FT dbSNP:rs199473621)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074457" FT VARIANT 1593 FT /note="I -> M (in LQT3; uncertain significance; FT dbSNP:rs199473276)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074749" FT VARIANT 1594 FT /note="F -> S (in LQT3; uncertain significance; FT dbSNP:rs199473277)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074750" FT VARIANT 1595 FT /note="D -> N (in PFHB1A; significant defect in the FT kinetics of fast-channel inactivation distinct from FT mutations reported in LQT3; dbSNP:rs137854607)" FT /evidence="ECO:0000269|PubMed:11804990" FT /id="VAR_017683" FT VARIANT 1596 FT /note="F -> I (in LQT3; uncertain significance; FT dbSNP:rs199473278)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074751" FT VARIANT 1604 FT /note="V -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473280)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074458" FT VARIANT 1609 FT /note="S -> W (in LQT3; dbSNP:rs199473622)" FT /evidence="ECO:0000269|PubMed:16922724" FT /id="VAR_036667" FT VARIANT 1613 FT /note="Q -> L (in BRGDA1; uncertain significance; FT dbSNP:rs199473281)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074459" FT VARIANT 1617 FT /note="Missing (in LQT3 and BRGDA1)" FT /evidence="ECO:0000269|PubMed:17081365, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055200" FT VARIANT 1620 FT /note="T -> K (in LQT3 and PFHB1A; dbSNP:rs199473282)" FT /id="VAR_055201" FT VARIANT 1620 FT /note="T -> M (in BRGDA1; arrhythmogenicity revealed only FT at temperatures approaching the physiologic range; FT dbSNP:rs199473282)" FT /evidence="ECO:0000269|PubMed:10532948, FT ECO:0000269|PubMed:10618304, ECO:0000269|PubMed:20129283, FT ECO:0000269|PubMed:9521325" FT /id="VAR_017684" FT VARIANT 1623 FT /note="R -> L (in LQT3; dbSNP:rs137854600)" FT /evidence="ECO:0000269|PubMed:10973849, FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:19716085" FT /id="VAR_009937" FT VARIANT 1623 FT /note="R -> Q (in LQT3 and BRGDA1; dbSNP:rs137854600)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:9506831, FT ECO:0000269|Ref.36" FT /id="VAR_001578" FT VARIANT 1626 FT /note="R -> H (in LQT3; uncertain significance; FT dbSNP:rs199473283)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074752" FT VARIANT 1626 FT /note="R -> P (in LQT3; uncertain significance; FT dbSNP:rs199473283)" FT /evidence="ECO:0000269|PubMed:16414944" FT /id="VAR_055202" FT VARIANT 1629 FT /note="R -> Q (in BRGDA1; changed voltage-gated sodium FT channel activity; no difference in current density but FT changed inactivation kinetics and prolonged recovery from FT inactivation; dbSNP:rs199473623)" FT /evidence="ECO:0000269|PubMed:20129283, FT ECO:0000269|PubMed:24167619" FT /id="VAR_074460" FT VARIANT 1642 FT /note="G -> E (in BRGDA1; uncertain significance; FT dbSNP:rs199473624)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074461" FT VARIANT 1644 FT /note="R -> C (in LQT3; dbSNP:rs199473287)" FT /evidence="ECO:0000269|PubMed:16414944, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055203" FT VARIANT 1644 FT /note="R -> H (in LQT3; dbSNP:rs28937316)" FT /evidence="ECO:0000269|PubMed:10973849, FT ECO:0000269|PubMed:15840476" FT /id="VAR_001579" FT VARIANT 1645 FT /note="T -> M (in LQT3; dbSNP:rs199473288)" FT /evidence="ECO:0000269|PubMed:10508990" FT /id="VAR_008958" FT VARIANT 1649 FT /note="A -> V (in BRGDA1; dbSNP:rs199473289)" FT /evidence="ECO:0000269|PubMed:17081365" FT /id="VAR_055204" FT VARIANT 1650 FT /note="L -> F (in LQT3; uncertain significance; FT dbSNP:rs199473290)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074753" FT VARIANT 1652 FT /note="M -> R (in LQT3; dbSNP:rs199473291)" FT /id="VAR_055205" FT VARIANT 1652 FT /note="M -> T (in LQT3; uncertain significance; FT dbSNP:rs199473291)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074754" FT VARIANT 1660 FT /note="I -> V (in BRGDA1 and LQT3; complete loss of sodium FT currents due to defective channel trafficking to the plasma FT membrane; dbSNP:rs199473625)" FT /evidence="ECO:0000269|PubMed:16414944, FT ECO:0000269|PubMed:17075016, ECO:0000269|PubMed:20129283" FT /id="VAR_055206" FT VARIANT 1661 FT /note="G -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473292)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074462" FT VARIANT 1667 FT /note="V -> I (in LQT3 and BRGDA1; dbSNP:rs199473293)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:20129283" FT /id="VAR_068338" FT VARIANT 1672 FT /note="S -> Y (in BRGDA1; uncertain significance; FT dbSNP:rs199473626)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074463" FT VARIANT 1680 FT /note="A -> T (in BRGDA1; uncertain significance; FT dbSNP:rs199473294)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074464" FT VARIANT 1690 FT /note="D -> N (in BRGDA1; decreased localization to the FT plasma membrane; decreased voltage-gated sodium channel FT activity; dominant negative effect; no effect on voltage FT dependence for activation and inactivation; FT dbSNP:rs1060499900)" FT /evidence="ECO:0000269|PubMed:23085483" FT /id="VAR_076557" FT VARIANT 1698 FT /note="A -> T (in BRGDA1; uncertain significance; FT dbSNP:rs199473295)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074465" FT VARIANT 1705 FT /note="F -> S (in SIDS; causes a hyperpolarizing shift of FT steady-state inactivation and delayed recovery from FT inactivation; dbSNP:rs199473627)" FT /evidence="ECO:0000269|PubMed:18596570" FT /id="VAR_055207" FT VARIANT 1709 FT /note="T -> M (in BRGDA1; uncertain significance; FT dbSNP:rs199473297)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074466" FT VARIANT 1709 FT /note="T -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473297)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074467" FT VARIANT 1710 FT /note="S -> L (in VF1; dbSNP:rs137854604)" FT /evidence="ECO:0000269|PubMed:10940383" FT /id="VAR_017685" FT VARIANT 1712 FT /note="G -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473298)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074468" FT VARIANT 1714 FT /note="D -> G (in BRGDA1; strong decrease of current FT density; does not affect ion selectivity properties; FT dbSNP:rs199473628)" FT /evidence="ECO:0000269|PubMed:16266370, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_026383" FT VARIANT 1722 FT /note="N -> D (in BRGDA1; uncertain significance; FT dbSNP:rs199473299)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074469" FT VARIANT 1723 FT /note="T -> N (in LQT3; uncertain significance; FT dbSNP:rs199473300)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074755" FT VARIANT 1728 FT /note="C -> R (in BRGDA1; uncertain significance; FT dbSNP:rs199473302)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074470" FT VARIANT 1728 FT /note="C -> W (in BRGDA1; uncertain significance; FT dbSNP:rs193922726)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074471" FT VARIANT 1739 FT /note="R -> W (in LQT3; uncertain significance; FT dbSNP:rs199473303)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074756" FT VARIANT 1740 FT /note="G -> R (in BRGDA1; dbSNP:rs199473304)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_026384" FT VARIANT 1743 FT /note="G -> E (in BRGDA1; dbSNP:rs199473629)" FT /evidence="ECO:0000269|PubMed:12106943, FT ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:20129283" FT /id="VAR_026385" FT VARIANT 1743 FT /note="G -> R (in BRGDA1; decreases expression at the cell FT membrane; yields nearly undetectable currents in FT transfected cells; dbSNP:rs199473305)" FT /evidence="ECO:0000269|PubMed:15023552, FT ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:23420830" FT /id="VAR_055208" FT VARIANT 1748 FT /note="G -> D (in BRGDA1; decreased localization to the FT plasma membrane; decreased voltage-gated sodium channel FT activity; dominant negative effect; changed voltage FT dependence for activation and inactivation)" FT /evidence="ECO:0000269|PubMed:23085483" FT /id="VAR_076558" FT VARIANT 1761 FT /note="L -> F (in LQT3; uncertain significance; FT dbSNP:rs199473307)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074757" FT VARIANT 1761 FT /note="L -> H (in LQT3; uncertain significance; FT dbSNP:rs199473308)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074758" FT VARIANT 1763 FT /note="V -> M (in LQT3; dbSNP:rs199473631)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055209" FT VARIANT 1764 FT /note="V -> F (in BRGDA1; uncertain significance; FT dbSNP:rs199473309)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074472" FT VARIANT 1766 FT /note="M -> L (in LQT3; affects protein trafficking; FT dbSNP:rs199473310)" FT /evidence="ECO:0000269|PubMed:12454206, FT ECO:0000269|PubMed:15840476" FT /id="VAR_055210" FT VARIANT 1767 FT /note="Y -> C (in LQT3; uncertain significance; FT dbSNP:rs199473632)" FT /evidence="ECO:0000269|PubMed:16414944" FT /id="VAR_074759" FT VARIANT 1768 FT /note="I -> V (in LQT3; increases the rate of recovery from FT inactivation and the channel availability, observed as a FT positive shift of the steady-state inactivation curve; FT dbSNP:rs199473311)" FT /evidence="ECO:0000269|PubMed:12209021" FT /id="VAR_055211" FT VARIANT 1777 FT /note="V -> M (in LQT3; dbSNP:rs199473314)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085" FT /id="VAR_055212" FT VARIANT 1779 FT /note="T -> M (in LQT3 and BRGDA1; dbSNP:rs199473634)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:20129283" FT /id="VAR_068339" FT VARIANT 1784 FT /note="E -> K (in LQT3 and BRGDA1; dbSNP:rs137854601)" FT /evidence="ECO:0000269|PubMed:10377081, FT ECO:0000269|PubMed:11901046, ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_008959" FT VARIANT 1787 FT /note="S -> N (in dbSNP:rs199473316)" FT /evidence="ECO:0000269|PubMed:10973849, FT ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:20129283" FT /id="VAR_009938" FT VARIANT 1790 FT /note="D -> G (in LQT3; dbSNP:rs199473317)" FT /evidence="ECO:0000269|PubMed:16414944, FT ECO:0000269|PubMed:9686753" FT /id="VAR_001580" FT VARIANT 1792 FT /note="D -> N (in SSS1; dbSNP:rs727504495)" FT /evidence="ECO:0000269|PubMed:22795782" FT /id="VAR_068475" FT VARIANT 1795 FT /note="Y -> C (in LQT3; also in a family associating LQT FT syndrome and atrial fibrillation; slows the onset of FT activation, but does not cause a marked negative shift in FT the voltage dependence of inactivation or affect the FT kinetics of the recovery from inactivation; increases the FT expression of sustained Na(+) channel activity and promotes FT entrance into an intermediate or slowly developing FT inactivated state; dbSNP:rs137854614)" FT /evidence="ECO:0000269|PubMed:11410597, FT ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:18929331, FT ECO:0000269|PubMed:19716085" FT /id="VAR_019123" FT VARIANT 1795 FT /note="Y -> H (in BRGDA1; accelerates the onset of FT activation and causes a marked negative shift in the FT voltage dependence of inactivation; does not affect the FT kinetics of the recovery from inactivation; increases the FT expression of sustained Na(+) channel activity and promotes FT entrance into an intermediate or slowly developing FT inactivated state; dbSNP:rs137854615)" FT /evidence="ECO:0000269|PubMed:11410597, FT ECO:0000269|PubMed:11901046" FT /id="VAR_019124" FT VARIANT 1795 FT /note="Y -> YD (in LQT3 and BRGDA1; 7.3-mV negative shift FT of the steady-state inactivation curve and 8.1-mV positive FT shift of the steady-state activation curve; may reduce FT sodium current during the upstroke of the action FT potential)" FT /evidence="ECO:0000269|PubMed:10590249, FT ECO:0000269|PubMed:11889015" FT /id="VAR_017686" FT VARIANT 1819 FT /note="D -> N (in LQT3; digenic; the patient also carries FT mutation G-100 on KCNH2; dbSNP:rs137854619)" FT /evidence="ECO:0000269|PubMed:16922724" FT /id="VAR_036668" FT VARIANT 1825 FT /note="L -> P (in LQT3; drug-induced LQT syndrome; FT dbSNP:rs79299226)" FT /id="VAR_055213" FT VARIANT 1826 FT /note="R -> C (in ATFB10; dbSNP:rs199473635)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055214" FT VARIANT 1826 FT /note="R -> H (in LQT3; sodium current characterized by FT slower decay and a 2- to 3-fold increase in late sodium FT current; dbSNP:rs137854610)" FT /evidence="ECO:0000269|PubMed:11710892, FT ECO:0000269|PubMed:19716085" FT /id="VAR_017687" FT VARIANT 1832 FT /note="Q -> E (in BRGDA1; uncertain significance; FT dbSNP:rs199473320)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074473" FT VARIANT 1836 FT /note="I -> T (in dbSNP:rs45563942)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074474" FT VARIANT 1839 FT /note="D -> G (in LQT3; dbSNP:rs199473321)" FT /evidence="ECO:0000269|PubMed:10627139, FT ECO:0000269|PubMed:19716085" FT /id="VAR_001581" FT VARIANT 1849 FT /note="H -> R (in LQT3; decreased interaction with FGF12, FT FGF13 and FGF14; increased voltage-gated sodium channel FT activity; altered inactivation; dbSNP:rs794728898)" FT /evidence="ECO:0000269|PubMed:26392562" FT /id="VAR_076559" FT VARIANT 1850 FT /note="C -> S (in BRGDA1; decreased I(Na) density; shift of FT the steady-state inactivation towards negative potentials; FT dbSNP:rs199473322)" FT /evidence="ECO:0000269|PubMed:18252757" FT /id="VAR_055215" FT VARIANT 1861 FT /note="V -> I (in BRGDA1; uncertain significance; FT dbSNP:rs199473636)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074475" FT VARIANT 1872 FT /note="K -> N (in BRGDA1; uncertain significance; FT dbSNP:rs199473323)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074476" FT VARIANT 1875 FT /note="M -> T (in atrial fibrillation; pronounced FT depolarized shift of the voltage dependence of steady-state FT inactivation; no persistent sodium current; FT dbSNP:rs199473324)" FT /evidence="ECO:0000269|PubMed:18929244" FT /id="VAR_055216" FT VARIANT 1897 FT /note="R -> W (in LQT3; uncertain significance; FT dbSNP:rs45465995)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074760" FT VARIANT 1901 FT /note="E -> K (in dbSNP:rs199473325)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074477" FT VARIANT 1901 FT /note="E -> Q (in LQT3; uncertain significance; FT dbSNP:rs199473325)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074761" FT VARIANT 1903 FT /note="V -> L (in BRGDA1; uncertain significance; FT dbSNP:rs864622270)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074478" FT VARIANT 1904 FT /note="S -> L (in LQT3; promotes late sodium currents by FT increasing the propensity of the channel to reopen during FT prolonged depolarization; dbSNP:rs150264233)" FT /evidence="ECO:0000269|PubMed:18708744" FT /id="VAR_055217" FT VARIANT 1909 FT /note="Q -> R (in LQT3; dbSNP:rs199473326)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068340" FT VARIANT 1913 FT /note="R -> H (in LQT3; uncertain significance; FT dbSNP:rs199473327)" FT /evidence="ECO:0000269|PubMed:16414944" FT /id="VAR_074762" FT VARIANT 1919 FT /note="R -> C (in dbSNP:rs199473328)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074479" FT VARIANT 1924 FT /note="A -> T (in BRGDA1; significantly affect cardiac FT sodium channel characteristics; associated with an increase FT in inward sodium current during the action potential FT upstroke; dbSNP:rs137854603)" FT /evidence="ECO:0000269|PubMed:10690282, FT ECO:0000269|PubMed:12106943, ECO:0000269|PubMed:19251209, FT ECO:0000269|PubMed:20129283" FT /id="VAR_017688" FT VARIANT 1935 FT /note="G -> S (in BRGDA1; uncertain significance; FT dbSNP:rs199473637)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_055218" FT VARIANT 1938 FT /note="E -> K (in BRGDA1; uncertain significance; FT dbSNP:rs199473329)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074480" FT VARIANT 1949 FT /note="A -> S (in LQT3; dbSNP:rs199473330)" FT /evidence="ECO:0000269|PubMed:15840476" FT /id="VAR_068341" FT VARIANT 1951 FT /note="V -> L (in BRGDA1, ATFB10 and LQT3; uncertain FT significance; dbSNP:rs41315493)" FT /evidence="ECO:0000269|PubMed:11901046, FT ECO:0000269|PubMed:18378609, ECO:0000269|PubMed:20129283" FT /id="VAR_026386" FT VARIANT 1951 FT /note="V -> M (in ATFB10; dbSNP:rs41315493)" FT /evidence="ECO:0000269|PubMed:18378609" FT /id="VAR_055219" FT VARIANT 1958 FT /note="R -> Q (found in a patient with long QT syndrome; FT uncertain significance; dbSNP:rs199473331)" FT /evidence="ECO:0000269|PubMed:15840476, FT ECO:0000269|PubMed:20129283" FT /id="VAR_068342" FT VARIANT 1962 FT /note="P -> L (in dbSNP:rs199473638)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074481" FT VARIANT 1968 FT /note="I -> M (in dbSNP:rs199473333)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074482" FT VARIANT 1968 FT /note="I -> S (in BRGDA1; dbSNP:rs199473639)" FT /id="VAR_055220" FT VARIANT 1977 FT /note="Y -> N (in LQT3; uncertain significance; FT dbSNP:rs199473334)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074763" FT VARIANT 1987 FT /note="N -> K (in ATFB10; dbSNP:rs199473335)" FT /evidence="ECO:0000269|PubMed:18088563" FT /id="VAR_065865" FT VARIANT 1991 FT /note="R -> Q (in dbSNP:rs199473336)" FT /evidence="ECO:0000269|PubMed:20129283" FT /id="VAR_074483" FT VARIANT 2004 FT /note="F -> L (in LQT3 and BRGDA1; also found in patients FT with atrial fibrillation; results in channels with FT decreased peak and persistent current amplitudes; increased FT closed-state and slow inactivation; decelerated recovery FT from inactivation; dbSNP:rs41311117)" FT /evidence="ECO:0000269|PubMed:18378609, FT ECO:0000269|PubMed:18456723, ECO:0000269|PubMed:20129283" FT /id="VAR_055221" FT VARIANT 2004 FT /note="F -> V (in BRGDA1 and LQT3; dbSNP:rs41311117)" FT /evidence="ECO:0000269|PubMed:19716085, FT ECO:0000269|PubMed:20129283" FT /id="VAR_074484" FT VARIANT 2006 FT /note="P -> A (found in a patient with long QT syndrome; FT uncertain significance; causes an increase of persistent FT sodium current and produces a depolarizing shift in voltage FT dependence of inactivation; dbSNP:rs45489199)" FT /evidence="ECO:0000269|PubMed:20129283, FT ECO:0000269|PubMed:21109022" FT /id="VAR_055222" FT VARIANT 2012 FT /note="R -> C (in LQT3; uncertain significance; FT dbSNP:rs199473640)" FT /evidence="ECO:0000269|PubMed:19716085" FT /id="VAR_074764" FT MUTAGEN 1476 FT /note="Q->K: Induces accelerated recovery from channel fast FT inactivation." FT /evidence="ECO:0000269|PubMed:16054936" FT MUTAGEN 1610 FT /note="D->A: Complete loss of channel inhibition by the FT spider Jingzhaotoxin-I." FT /evidence="ECO:0000269|PubMed:26721415" FT MUTAGEN 1610 FT /note="D->R: High decrease in affinity to the sea anemone FT toxin anthopleurin-B." FT /evidence="ECO:0000269|PubMed:24898004" FT MUTAGEN 1614 FT /note="K->A: 4.2-fold decrease of channel inhibition FT potency by the spider Jingzhaotoxin-I." FT /evidence="ECO:0000269|PubMed:26721415" FT MUTAGEN 1802..1804 FT /note="DPE->APA: Abolishes calcium response on channel FT inactivation." FT /evidence="ECO:0000269|PubMed:19074138" FT MUTAGEN 1974 FT /note="P->A: Strongly reduces interaction with NEDD4, FT NEDD4L or WWP2." FT /evidence="ECO:0000269|PubMed:15548568" FT MUTAGEN 1975 FT /note="P->A: Strongly reduces interaction with NEDD4, FT NEDD4L or WWP2." FT /evidence="ECO:0000269|PubMed:15548568" FT MUTAGEN 1976 FT /note="S->A: Strongly reduces interaction with NEDD4, FT NEDD4L or WWP2." FT /evidence="ECO:0000269|PubMed:15548568" FT MUTAGEN 1977 FT /note="Y->A: Strongly reduces interaction with NEDD4, FT NEDD4L or WWP2." FT /evidence="ECO:0000269|PubMed:15217910, FT ECO:0000269|PubMed:15548568" FT MUTAGEN 1978 FT /note="D->A: No effect on interaction with NEDD4, NEDD4L or FT WWP2." FT /evidence="ECO:0000269|PubMed:15548568" FT MUTAGEN 1979 FT /note="S->A: No effect on interaction with NEDD4, NEDD4L or FT WWP2." FT /evidence="ECO:0000269|PubMed:15548568" FT MUTAGEN 1980 FT /note="V->A: No effect on interaction with NEDD4, NEDD4L or FT WWP2." FT /evidence="ECO:0000269|PubMed:15217910, FT ECO:0000269|PubMed:15548568" FT MUTAGEN 1980 FT /note="V->D,R: Strongly reduces interaction with NEDD4L." FT /evidence="ECO:0000269|PubMed:15217910, FT ECO:0000269|PubMed:15548568" FT CONFLICT 91 FT /note="K -> R (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 96 FT /note="L -> P (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 120 FT /note="I -> V (in Ref. 1; AAA58644)" FT /evidence="ECO:0000305" FT CONFLICT 162 FT /note="Y -> H (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 180 FT /note="G -> A (in Ref. 1; AAA58644)" FT /evidence="ECO:0000305" FT CONFLICT 181 FT /note="F -> S (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 191 FT /note="D -> G (in Ref. 5; BAD12084/BAD12085 and 6; FT ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 196 FT /note="L -> P (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 215 FT /note="V -> L (in Ref. 5; BAD12084/BAD12085, 6; FT ABR15763/ABR15764 and 9; AAI44622/AAI40814)" FT /evidence="ECO:0000305" FT CONFLICT 234 FT /note="S -> P (in Ref. 5; BAD12084/BAD12085, 6; FT ABR15763/ABR15764 and 9; AAI44622/AAI40814)" FT /evidence="ECO:0000305" FT CONFLICT 280 FT /note="C -> R (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 290 FT /note="T -> I (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 516 FT /note="S -> N (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 608 FT /note="D -> N (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 618 FT /note="L -> I (in Ref. 4; AAO91669)" FT /evidence="ECO:0000305" FT CONFLICT 653 FT /note="F -> V (in Ref. 5; BAD12084/BAD12085)" FT /evidence="ECO:0000305" FT CONFLICT 918 FT /note="V -> G (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 987 FT /note="Q -> H (in Ref. 1; AAA58644, 5; BAD12084/BAD12085 FT and 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 1085 FT /note="G -> W (in Ref. 1; AAA58644 and 5; BAD12084)" FT /evidence="ECO:0000305" FT CONFLICT 1087 FT /note="E -> R (in Ref. 1; AAA58644 and 5; BAD12084)" FT /evidence="ECO:0000305" FT CONFLICT 1088 FT /note="A -> G (in Ref. 1; AAA58644 and 5; BAD12084)" FT /evidence="ECO:0000305" FT CONFLICT 1342 FT /note="L -> H (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 1479 FT /note="K -> T (in Ref. 5; BAD12084/BAD12085)" FT /evidence="ECO:0000305" FT CONFLICT 1480..1481 FT /note="LG -> IR (in Ref. 7; ABQ01244)" FT /evidence="ECO:0000305" FT CONFLICT 1616 FT /note="F -> S (in Ref. 10; BAD92103)" FT /evidence="ECO:0000305" FT CONFLICT 1657 FT /note="L -> P (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT CONFLICT 1850 FT /note="C -> R (in Ref. 6; ABR15763/ABR15764)" FT /evidence="ECO:0000305" FT HELIX 121..128 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 131..148 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 157..178 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 185..191 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 193..207 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 218..223 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 224..227 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 228..231 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 232..235 FT /evidence="ECO:0007829|PDB:7DTC" FT HELIX 236..250 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 253..272 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 273..276 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 288..292 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 294..302 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 304..307 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 318..320 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 328..332 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 339..342 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 349..351 FT /evidence="ECO:0007829|PDB:7DTC" FT STRAND 355..357 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 358..369 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 370..373 FT /evidence="ECO:0007829|PDB:7DTC" FT HELIX 374..385 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 390..399 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 401..428 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 700..714 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 717..720 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 721..734 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 738..740 FT /evidence="ECO:0007829|PDB:7DTC" FT HELIX 745..770 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 773..776 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 780..782 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 783..797 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 806..812 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 813..819 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 825..835 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 836..838 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 842..861 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 862..864 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 865..868 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 872..874 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 884..896 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 900..910 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 912..942 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1191..1203 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1205..1220 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1221..1224 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1230..1232 FT /evidence="ECO:0007829|PDB:7DTC" FT HELIX 1233..1267 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1269..1271 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1272..1290 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1299..1303 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1304..1315 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1318..1329 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1332..1356 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1361..1364 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1366..1368 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1375..1377 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1381..1386 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1394..1397 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1402..1404 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1405..1416 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1422..1429 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1433..1436 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1440..1443 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1444..1446 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1447..1477 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1480..1482 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1491..1500 FT /evidence="ECO:0007829|PDB:4DJC" FT STRAND 1501..1504 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1516..1526 FT /evidence="ECO:0007829|PDB:5DBR" FT HELIX 1528..1546 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1554..1581 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1583..1586 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1589..1591 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1592..1608 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1609..1614 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1621..1626 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1627..1635 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1636..1639 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1641..1651 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1654..1678 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1679..1681 FT /evidence="ECO:0007829|PDB:7DTC" FT STRAND 1690..1696 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1697..1708 FT /evidence="ECO:0007829|PDB:6LQA" FT TURN 1709..1713 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1714..1720 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1724..1727 FT /evidence="ECO:0007829|PDB:6LQA" FT STRAND 1735..1737 FT /evidence="ECO:0007829|PDB:7DTC" FT HELIX 1745..1780 FT /evidence="ECO:0007829|PDB:6LQA" FT HELIX 1788..1801 FT /evidence="ECO:0007829|PDB:4DCK" FT STRAND 1807..1810 FT /evidence="ECO:0007829|PDB:4DCK" FT HELIX 1811..1813 FT /evidence="ECO:0007829|PDB:4DCK" FT HELIX 1814..1820 FT /evidence="ECO:0007829|PDB:4DCK" FT TURN 1823..1825 FT /evidence="ECO:0007829|PDB:4DCK" FT HELIX 1832..1837 FT /evidence="ECO:0007829|PDB:4DCK" FT STRAND 1841..1843 FT /evidence="ECO:0007829|PDB:4DCK" FT TURN 1844..1846 FT /evidence="ECO:0007829|PDB:4DCK" FT STRAND 1847..1849 FT /evidence="ECO:0007829|PDB:4DCK" FT HELIX 1850..1862 FT /evidence="ECO:0007829|PDB:4DCK" FT HELIX 1866..1882 FT /evidence="ECO:0007829|PDB:4DCK" FT HELIX 1886..1888 FT /evidence="ECO:0007829|PDB:4DCK" FT STRAND 1891..1894 FT /evidence="ECO:0007829|PDB:4OVN" FT HELIX 1896..1926 FT /evidence="ECO:0007829|PDB:4DCK" SQ SEQUENCE 2016 AA; 226940 MW; 841E3A365931190B CRC64; MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSTTLQ ESREGLPEEE APRPQLDLQA SKKLPDLYGN PPQELIGEPL EDLDPFYSTQ KTFIVLNKGK TIFRFSATNA LYVLSPFHPI RRAAVKILVH SLFNMLIMCT ILTNCVFMAQ HDPPPWTKYV EYTFTAIYTF ESLVKILARG FCLHAFTFLR DPWNWLDFSV IIMAYTTEFV DLGNVSALRT FRVLRALKTI SVISGLKTIV GALIQSVKKL ADVMVLTVFC LSVFALIGLQ LFMGNLRHKC VRNFTALNGT NGSVEADGLV WESLDLYLSD PENYLLKNGT SDVLLCGNSS DAGTCPEGYR CLKAGENPDH GYTSFDSFAW AFLALFRLMT QDCWERLYQQ TLRSAGKIYM IFFMLVIFLG SFYLVNLILA VVAMAYEEQN QATIAETEEK EKRFQEAMEM LKKEHEALTI RGVDTVSRSS LEMSPLAPVN SHERRSKRRK RMSSGTEECG EDRLPKSDSE DGPRAMNHLS LTRGLSRTSM KPRSSRGSIF TFRRRDLGSE ADFADDENST AGESESHHTS LLVPWPLRRT SAQGQPSPGT SAPGHALHGK KNSTVDCNGV VSLLGAGDPE ATSPGSHLLR PVMLEHPPDT TTPSEEPGGP QMLTSQAPCV DGFEEPGARQ RALSAVSVLT SALEELEESR HKCPPCWNRL AQRYLIWECC PLWMSIKQGV KLVVMDPFTD LTITMCIVLN TLFMALEHYN MTSEFEEMLQ VGNLVFTGIF TAEMTFKIIA LDPYYYFQQG WNIFDSIIVI LSLMELGLSR MSNLSVLRSF RLLRVFKLAK SWPTLNTLIK IIGNSVGALG NLTLVLAIIV FIFAVVGMQL FGKNYSELRD SDSGLLPRWH MMDFFHAFLI IFRILCGEWI ETMWDCMEVS GQSLCLLVFL LVMVIGNLVV LNLFLALLLS SFSADNLTAP DEDREMNNLQ LALARIQRGL RFVKRTTWDF CCGLLRQRPQ KPAALAAQGQ LPSCIATPYS PPPPETEKVP PTRKETRFEE GEQPGQGTPG DPEPVCVPIA VAESDTDDQE EDEENSLGTE EESSKQQESQ PVSGGPEAPP DSRTWSQVSA TASSEAEASA SQADWRQQWK AEPQAPGCGE TPEDSCSEGS TADMTNTAEL LEQIPDLGQD VKDPEDCFTE GCVRRCPCCA VDTTQAPGKV WWRLRKTCYH IVEHSWFETF IIFMILLSSG ALAFEDIYLE ERKTIKVLLE YADKMFTYVF VLEMLLKWVA YGFKKYFTNA WCWLDFLIVD VSLVSLVANT LGFAEMGPIK SLRTLRALRP LRALSRFEGM RVVVNALVGA IPSIMNVLLV CLIFWLIFSI MGVNLFAGKF GRCINQTEGD LPLNYTIVNN KSQCESLNLT GELYWTKVKV NFDNVGAGYL ALLQVATFKG WMDIMYAAVD SRGYEEQPQW EYNLYMYIYF VIFIIFGSFF TLNLFIGVII DNFNQQKKKL GGQDIFMTEE QKKYYNAMKK LGSKKPQKPI PRPLNKYQGF IFDIVTKQAF DVTIMFLICL NMVTMMVETD DQSPEKINIL AKINLLFVAI FTGECIVKLA ALRHYYFTNS WNIFDFVVVI LSIVGTVLSD IIQKYFFSPT LFRVIRLARI GRILRLIRGA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI YSIFGMANFA YVKWEAGIDD MFNFQTFANS MLCLFQITTS AGWDGLLSPI LNTGPPYCDP TLPNSNGSRG DCGSPAVGIL FFTTYIIISF LIVVNMYIAI ILENFSVATE ESTEPLSEDD FDMFYEIWEK FDPEATQFIE YSVLSDFADA LSEPLRIAKP NQISLINMDL PMVSGDRIHC MDILFAFTKR VLGESGEMDA LKIQMEEKFM AANPSKISYE PITTTLRRKH EEVSAMVIQR AFRRHLLQRS LKHASFLFRQ QAGSGLSEED APEREGLIAY VMSENFSRPL GPPSSSSISS TSFPPSYDSV TRATSDNLQV RGSDYSHSED LADFPPSPDR DRESIV //