Paralogue Annotation for SCN5A residue 439

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 439
Reference Amino Acid: E - Glutamate
Protein Domain: Interdomain Linker I-II


Paralogue Variants mapped to SCN5A residue 439

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CACNA1AR387GEpisodic ataxia 2Low3 27066515

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.



SCN5AAVVAMAYEEQNQATIAETEEK-EKRFQEAM>E<MLKK------------EHEALTIRGVDTVS457
SCN1AAVVAMAYEEQNQATLEEAEQK-EAEFQQMI>E<QLKK------------QQEAAQQAATATAS467
SCN2AAVVAMAYEEQNQATLEEAEQK-EAEFQQML>E<QLKK------------QQEEAQAAAAAASA469
SCN3AAVVAMAYEEQNQATLEEAEQK-EAEFQQML>E<QLKK------------QQEEAQAVAAASAA468
SCN4AAVVAMAYAEQNEATLAEDKEK-EEEFQQML>E<KFKK------------HQEELEKAKAAQAL491
SCN7AGILAMAYEEEKQRVGEISKKI-EPKFQQTG>K<ELQE------------GNETDEAK------432
SCN8AAVVAMAYEEQNQATLEEAEQK-EAEFKAML>E<QLKK------------QQEEAQAAAMATSA455
SCN9AAVVAMAYEEQNQANIEEAKQK-ELEFQQML>D<RLKK------------EQEEAEAIAAAAAE446
SCN10AAVVTMAYEEQNQATTDEIEAK-EKKFQEAL>E<MLRK------------EQEVLAALGIDTTS441
SCN11AAVVTMAYEEQNKNVAAEIEAK-EKMFQEAQ>Q<LLKE------------EKEALVAMGIDRSS444
CACNA1AGVLSGEFAKERERVENRRAFLKLRRQQQIE>R<ELNG------------YMEWISKA-EE---401
CACNA1BGVLSGEFAKERERVENRRAFLKLRRQQQIE>R<ELNG------------YLEWIFKA-EE---397
CACNA1CGVLSGEFSKEREKAKARGDFQKLREKQQLE>E<DLKG------------YLDWITQA-ED---446
CACNA1DGVLSGEFSKEREKAKARGDFQKLREKQQLE>E<DLKG------------YLDWITQA-ED---447
CACNA1EGVLSGEFAKERERVENRRAFMKLRRQQQIE>R<ELNG------------YRAWIDKA-EE---392
CACNA1FGVLSGEFSKEREKAKARGDFQKQREKQQME>E<DLRG------------YLDWITQA-EE---413
CACNA1GVVIATQFSETKQRESQLMREQRVRFLSNAS>T<LASFSEPGSCYEELLKYLVYILRKAAR---449
CACNA1HVVIATQFSETKQRESQLMREQRARHLSNDS>T<LASFSEPGSCYEELLKYVGHIFRKVKR---473
CACNA1IVVIATQFSETKQREHRLMLEQRQRYLS-SS>T<VASYAEPGDCYEEIFQYVCHILRKAKR---451
CACNA1SGVLSGEFTKEREKAKSRGTFQKLREKQQLD>E<DLRG------------YMSWITQG-EV---375
cons                              > <                              

See full Alignment of Paralogues


Known Variants in SCN5A

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.E439Kc.1315G>A Inherited ArrhythmiaBrSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited 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 Brugada syndrome disease phenotype explained in apparently benign sodium channel mutations. Circ Cardiovasc Genet. 2014 7(2):123-31. doi: 10.1161/CIRCGENETICS.113.000292. 24573164