Paralogue Annotation for SCN5A residue 411

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 411
Reference Amino Acid: V - Valine
Protein Domain: TM Domain 1


Paralogue Variants mapped to SCN5A residue 411

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN4AV445MMyotoniaHigh9 9392583, 22653516, 25839108, 25724373
SCN9AV400MErythermalgia, carbamazepine-responsiveHigh9 19557861, 26920677

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.



SCN5ALRSAGKIY-MIFFMLVIFLGSFYLVNLILA>V<VAMAYEEQNQATIAETEEK-EKRFQEAMEM440
SCN1ALRAAGKTY-MIFFVLVIFLGSFYLINLILA>V<VAMAYEEQNQATLEEAEQK-EAEFQQMIEQ450
SCN2ALRAAGKTY-MIFFVLVIFLGSFYLINLILA>V<VAMAYEEQNQATLEEAEQK-EAEFQQMLEQ452
SCN3ALRAAGKTY-MIFFVLVIFLGSFYLVNLILA>V<VAMAYEEQNQATLEEAEQK-EAEFQQMLEQ451
SCN4ALRAAGKTY-MIFFVVIIFLGSFYLINLILA>V<VAMAYAEQNEATLAEDKEK-EEEFQQMLEK474
SCN7ALYASGKVY-MIFFVVVSFLFSFYMASLFLG>I<LAMAYEEEKQRVGEISKKI-EPKFQQTGKE421
SCN8ALRAAGKTY-MIFFVLVIFVGSFYLVNLILA>V<VAMAYEEQNQATLEEAEQK-EAEFKAMLEQ438
SCN9ALRAAGKTY-MIFFVVVIFLGSFYLINLILA>V<VAMAYEEQNQANIEEAKQK-ELEFQQMLDR429
SCN10ALRTSGKIY-MIFFVLVIFLGSFYLVNLILA>V<VTMAYEEQNQATTDEIEAK-EKKFQEALEM424
SCN11ALRTTGLYS-VFFFIVVIFLGSFYLINLTLA>V<VTMAYEEQNKNVAAEIEAK-EKMFQEAQQL427
CACNA1ANDASGNTWNWLYFIPLIIIGSFFMLNLVLG>V<LSGEFAKERERVENRRAFLKLRRQQQIERE388
CACNA1BNDAAGNTWNWLYFIPLIIIGSFFMLNLVLG>V<LSGEFAKERERVENRRAFLKLRRQQQIERE384
CACNA1CNDAVGRDWPWIYFVTLIIIGSFFVLNLVLG>V<LSGEFSKEREKAKARGDFQKLREKQQLEED433
CACNA1DNDAIGWEWPWVYFVSLIILGSFFVLNLVLG>V<LSGEFSKEREKAKARGDFQKLREKQQLEED434
CACNA1ENDALGATWNWLYFIPLIIIGSFFVLNLVLG>V<LSGEFAKERERVENRRAFMKLRRQQQIERE379
CACNA1FQDAMGYELPWVYFVSLVIFGSFFVLNLVLG>V<LSGEFSKEREKAKARGDFQKQREKQQMEED400
CACNA1GMDAHSF-YNFIYFILLIIVGSFFMINLCLV>V<IATQFSETKQRESQLMREQRVRFLSNASTL423
CACNA1HMDAHSF-YNFIYFILLIIVGSFFMINLCLV>V<IATQFSETKQRESQLMREQRARHLSNDSTL447
CACNA1IMDAHSF-YNFIYFILLIIVGSFFMINLCLV>V<IATQFSETKQREHRLMLEQRQRYLS-SSTV425
CACNA1SNDAIGNEWPWIYFVTLILLGSFFILNLVLG>V<LSGEFTKEREKAKSRGTFQKLREKQQLDED362
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.V411Mc.1231G>A Inherited ArrhythmiaLQTSrs72549410SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation. 2000 102(9):945-7. 10961955
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
Other Cardiac Phenotype High-efficiency multiplex capillary electrophoresis single strand conformation polymorphism (multi-CE-SSCP) mutation screening of SCN5A: a rapid genetic approach to cardiac arrhythmia. Clin Genet. 2006 69(6):504-11. 16712702
Inherited ArrhythmiaLQTS Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085
Inherited ArrhythmiaLQTS A novel mechanism for LQT3 with 2:1 block: a pore-lining mutation in Nav1.5 significantly affects voltage-dependence of activation. Heart Rhythm. 2011 8(5):770-7. 21193062
Inherited ArrhythmiaLQTS Flecainide, a therapeutic option in a patient with long QT syndrome type 3 caused by the heterozygous V411M mutation in the SCN5A gene. Rev Esp Cardiol (Engl Ed). 2012 65(11):1058-9. doi: 10.1016/j.recesp.2012.03.014. 22721569