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

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CACNA1A	R387G	Episodic ataxia 2	Low	3	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.

SCN5A	AVVAMAYEEQNQATIAETEEK-EKRFQEAM>E<MLKK------------EHEALTIRGVDTVS	457
SCN1A	AVVAMAYEEQNQATLEEAEQK-EAEFQQMI>E<QLKK------------QQEAAQQAATATAS	467
SCN2A	AVVAMAYEEQNQATLEEAEQK-EAEFQQML>E<QLKK------------QQEEAQAAAAAASA	469
SCN3A	AVVAMAYEEQNQATLEEAEQK-EAEFQQML>E<QLKK------------QQEEAQAVAAASAA	468
SCN4A	AVVAMAYAEQNEATLAEDKEK-EEEFQQML>E<KFKK------------HQEELEKAKAAQAL	491
SCN7A	GILAMAYEEEKQRVGEISKKI-EPKFQQTG>K<ELQE------------GNETDEAK------	432
SCN8A	AVVAMAYEEQNQATLEEAEQK-EAEFKAML>E<QLKK------------QQEEAQAAAMATSA	455
SCN9A	AVVAMAYEEQNQANIEEAKQK-ELEFQQML>D<RLKK------------EQEEAEAIAAAAAE	446
SCN10A	AVVTMAYEEQNQATTDEIEAK-EKKFQEAL>E<MLRK------------EQEVLAALGIDTTS	441
SCN11A	AVVTMAYEEQNKNVAAEIEAK-EKMFQEAQ>Q<LLKE------------EKEALVAMGIDRSS	444
CACNA1A	GVLSGEFAKERERVENRRAFLKLRRQQQIE>R<ELNG------------YMEWISKA-EE---	401
CACNA1B	GVLSGEFAKERERVENRRAFLKLRRQQQIE>R<ELNG------------YLEWIFKA-EE---	397
CACNA1C	GVLSGEFSKEREKAKARGDFQKLREKQQLE>E<DLKG------------YLDWITQA-ED---	446
CACNA1D	GVLSGEFSKEREKAKARGDFQKLREKQQLE>E<DLKG------------YLDWITQA-ED---	447
CACNA1E	GVLSGEFAKERERVENRRAFMKLRRQQQIE>R<ELNG------------YRAWIDKA-EE---	392
CACNA1F	GVLSGEFSKEREKAKARGDFQKQREKQQME>E<DLRG------------YLDWITQA-EE---	413
CACNA1G	VVIATQFSETKQRESQLMREQRVRFLSNAS>T<LASFSEPGSCYEELLKYLVYILRKAAR---	449
CACNA1H	VVIATQFSETKQRESQLMREQRARHLSNDS>T<LASFSEPGSCYEELLKYVGHIFRKVKR---	473
CACNA1I	VVIATQFSETKQREHRLMLEQRQRYLS-SS>T<VASYAEPGDCYEEIFQYVCHILRKAKR---	451
CACNA1S	GVLSGEFTKEREKAKSRGTFQKLREKQQLD>E<DLRG------------YMSWITQG-EV---	375
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.E439K	c.1315G>A	Inherited Arrhythmia	BrS	rs199473570	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	BrS	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
Reports		Inherited Arrhythmia	BrS	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