Paralogue Annotation for SCN5A residue 406

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 406
Reference Amino Acid: N - Asparagine
Protein Domain: TM Domain 1


Paralogue Variants mapped to SCN5A residue 406

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
SCN9AN395KErythermalgia, primaryHigh9 15955112, 17430993
SCN9AN395KErythermalgia, primaryHigh9 17263810
SCN4AN440KMyotoniaHigh9 22106717, 22914841

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.



SCN5ALYQQTLRSAGKIY-MIFFMLVIFLGSFYLV>N<LILAVVAMAYEEQNQATIAETEEK-EKRFQ435
SCN1ALYQLTLRAAGKTY-MIFFVLVIFLGSFYLI>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFQ445
SCN2ALYQLTLRAAGKTY-MIFFVLVIFLGSFYLI>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFQ447
SCN3ALYQLTLRAAGKTY-MIFFVLVIFLGSFYLV>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFQ446
SCN4ALFQLTLRAAGKTY-MIFFVVIIFLGSFYLI>N<LILAVVAMAYAEQNEATLAEDKEK-EEEFQ469
SCN7ALYHQILYASGKVY-MIFFVVVSFLFSFYMA>S<LFLGILAMAYEEEKQRVGEISKKI-EPKFQ416
SCN8ALYQLTLRAAGKTY-MIFFVLVIFVGSFYLV>N<LILAVVAMAYEEQNQATLEEAEQK-EAEFK433
SCN9ALYQQTLRAAGKTY-MIFFVVVIFLGSFYLI>N<LILAVVAMAYEEQNQANIEEAKQK-ELEFQ424
SCN10ALYQQTLRTSGKIY-MIFFVLVIFLGSFYLV>N<LILAVVTMAYEEQNQATTDEIEAK-EKKFQ419
SCN11ALYQQTLRTTGLYS-VFFFIVVIFLGSFYLI>N<LTLAVVTMAYEEQNKNVAAEIEAK-EKMFQ422
CACNA1ALLYNSNDASGNTWNWLYFIPLIIIGSFFML>N<LVLGVLSGEFAKERERVENRRAFLKLRRQQ383
CACNA1BILYNTNDAAGNTWNWLYFIPLIIIGSFFML>N<LVLGVLSGEFAKERERVENRRAFLKLRRQQ379
CACNA1CVLYWVNDAVGRDWPWIYFVTLIIIGSFFVL>N<LVLGVLSGEFSKEREKAKARGDFQKLREKQ428
CACNA1DVLYWVNDAIGWEWPWVYFVSLIILGSFFVL>N<LVLGVLSGEFSKEREKAKARGDFQKLREKQ429
CACNA1EVLYNTNDALGATWNWLYFIPLIIIGSFFVL>N<LVLGVLSGEFAKERERVENRRAFMKLRRQQ374
CACNA1FVLYWMQDAMGYELPWVYFVSLVIFGSFFVL>N<LVLGVLSGEFSKEREKAKARGDFQKQREKQ395
CACNA1GIMYFVMDAHSF-YNFIYFILLIIVGSFFMI>N<LCLVVIATQFSETKQRESQLMREQRVRFLS418
CACNA1HIMYYVMDAHSF-YNFIYFILLIIVGSFFMI>N<LCLVVIATQFSETKQRESQLMREQRARHLS442
CACNA1IIMYYVMDAHSF-YNFIYFILLIIVGSFFMI>N<LCLVVIATQFSETKQREHRLMLEQRQRYLS421
CACNA1SVLYWVNDAIGNEWPWIYFVTLILLGSFFIL>N<LVLGVLSGEFTKEREKAKSRGTFQKLREKQ357
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.N406Kc.1218C>G Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited 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
p.N406Sc.1217A>G Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaBrS A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs. J Cardiovasc Electrophysiol. 2005 16(5):486-93. 15877619
Inherited ArrhythmiaBrS A paradoxical effect of lidocaine for the N406S mutation of SCN5A associated with Brugada syndrome. Int J Cardiol. 2007 121(3):239-48. 17445919
Inherited ArrhythmiaBrS Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A. J Cardiovasc Electrophysiol. 2005 16(4):378-83. 15828879
p.N406Kc.1218C>A Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: possibly damaging
ReportsInherited 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 ArrhythmiaLQTS Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: from the cradle to the bench. J Cardiovasc Electrophysiol. 2014 25(1):66-73. doi: 10.1111/jce.12270. 24112685