Paralogue Annotation for SCN5A residue 1225

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1225
Reference Amino Acid: E - Glutamate
Protein Domain: TM Domain 3


Paralogue Variants mapped to SCN5A residue 1225

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN1AE1238DMyoclonic epilepsy of infancyHigh9 17347258

To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in SCN5A.



SCN5ARKTCYHIVEHSWFETFIIFMILLSSGALAF>E<DIYLEERKTIKVLLEYADKMFTYVFVLEML1255
SCN1ARRTCFRIVEHNWFETFIVFMILLSSGALAF>E<DIYIDQRKTIKTMLEYADKVFTYIFILEML1268
SCN2ARKTCYKIVEHNWFETFIVFMILLSSGALAF>E<DIYIEQRKTIKTMLEYADKVFTYIFILEML1258
SCN3ARKTCYSIVEHNWFETFIVFMILLSSGALAF>E<DIYIEQRKTIKTMLEYADKVFTYIFILEML1256
SCN4ARRACFKIVEHNWFETFIVFMILLSSGALAF>E<DIYIEQRRVIRTILEYADKVFTYIFIMEML1081
SCN7ARKTCCKIVENNWFKCFIGLVTLLSTGTLAF>E<DIYMDQRKTIKILLEYADMIFTYIFILEML984
SCN8ARKTCFLIVEHNWFETFIIFMILLSSGALAF>E<DIYIEQRKTIRTILEYADKVFTYIFILEML1248
SCN9ARKTCYKIVEHSWFESFIVLMILLSSGALAF>E<DIYIERKKTIKIILEYADKIFTYIFILEML1231
SCN10ARKTCYRIVEHSWFESFIIFMILLSSGSLAF>E<DYYLDQKPTVKALLEYTDRVFTFIFVFEML1202
SCN11ARKTCYQIVKHSWFESFIIFVILLSSGALIF>E<DVHLENQPKIQELLNCTDIIFTHIFILEMV1106
CACNA1ARRLCHYILNLRYFEMCILMVIAMSSIALAA>E<DPV-QPNAPRNNVLRYFDYVFTGVFTFEMV1293
CACNA1BRRFCHYIVTMRYFEVVILVVIALSSIALAA>E<DPV-RTDSPRNNALKYLDYIFTGVFTFEMV1200
CACNA1CRLQCHRIVNDTIFTNLILFFILLSSISLAA>E<DPV-QHTSFRNHILFYFDIVFTTIFTIEIA949
CACNA1DRVGCHKLINHHIFTNLILVFIMLSSAALAA>E<DPI-RSHSFRNTILGYFDYAFTAIFTVEIL955
CACNA1ERRACHYIVNLRYFEMCILLVIAASSIALAA>E<DPV-LTNSERNKVLRYFDYVFTGVFTFEMV1202
CACNA1FRKGCHTLIHHHVFTNLILVFIILSSVSLAA>E<DPI-RAHSFRNHILGYFDYAFTSIFTVEIL920
CACNA1GRLLCHRIITHKMFDHVVLVIIFLNCITIAM>E<RPKIDPHSAERIFLTLSNYIFTAVFLAEMT1326
CACNA1HRVSCQKVITHKMFDHVVLVFIFLNCVTIAL>E<RPDIDPGSTERVFLSVSNYIFTAIFVAEMM1344
CACNA1IRVLCQTIIAHKLFDYVVLAFIFLNCITIAL>E<RPQIEAGSTERIFLTVSNYIFTAIFVGEMT1220
CACNA1SRVLCHRIVNATWFTNFILLFILLSSAALAA>E<DPI-RADSMRNQILKHFDIGFTSVFTVEIV848
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.E1225Kc.3673G>A Inherited ArrhythmiaLQTS,BrSrs199473204SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaBrS Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol. 2002 40(2):350-6. 12106943
Inherited ArrhythmiaBrS Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease. Hum Mutat. 2003 21(6):651-2. 14961552
Inherited ArrhythmiaLQTS Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476
Inherited ArrhythmiaBrS An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 7(1):33-46. 20129283
Inherited ArrhythmiaBrS The genetic basis of Brugada syndrome: a mutation update. Hum Mutat. 2009 30(9):1256-66. 19606473
Inherited ArrhythmiaBrS Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. J Med Genet. 2014 51(1):35-44. doi: 10.1136/jmedgenet-2013-101917. 24136861