Paralogue Annotation for SCN5A residue 1525

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1525
Reference Amino Acid: V - Valine
Protein Domain: TM Domain 4

Paralogue Variants mapped to SCN5A residue 1525

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	V1538I	Dravet syndrome	High	9	18930999, 24066114

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	SKKP--------QKPIPRPLNKYQGFIFDI>V<TKQAFDVTIMFLICLNMVTMMVETDDQSPE	1555
SCN1A	SKKP--------QKPIPRPGNKFQGMVFDF>V<TRQVFDISIMILICLNMVTMMVETDDQSEY	1568
SCN2A	SKKP--------QKPIPRPANKFQGMVFDF>V<TKQVFDISIMILICLNMVTMMVETDDQSQE	1558
SCN3A	SKKP--------QKPIPRPANKFQGMVFDF>V<TRQVFDISIMILICLNMVTMMVETDDQGKY	1553
SCN4A	SKKP--------QKPIPRPQNKIQGMVYDL>V<TKQAFDITIMILICLNMVTMMVETDNQSQL	1380
SCN7A	YEDS--------QRPVPRPLNKLQGFIFDV>V<TSQAFNVIVMVLICFQAIAMMIDTDVQSLQ	1278
SCN8A	SKKP--------QKPIPRPLNKIQGIVFDF>V<TQQAFDIVIMMLICLNMVTMMVETDTQSKQ	1549
SCN9A	SKKP--------QKPIPRPGNKIQGCIFDL>V<TNQAFDISIMVLICLNMVTMMVEKEGQSQH	1531
SCN10A	SKKP--------QKPIPRPLNKFQGFVFDI>V<TRQAFDITIMVLICLNMITMMVETDDQSEE	1503
SCN11A	SKKP--------QKPIPRPLNKCQGLVFDI>V<TSQIFDIIIISLIILNMISMMAESYNQPKA	1393
CACNA1A	SAKP-------LTRHMPQNKQSFQYRMWQF>V<VSPPFEYTIMAMIALNTIVLMMKFYGASVA	1593
CACNA1B	SAKP-------LTRYMPQNRQSFQYKTWTF>V<VSPPFEYFIMAMIALNTVVLMMKFYDAPYE	1499
CACNA1C	KARP-------LRRYIPK--NQHQYKVWYV>V<NSTYFEYLMFVLILLNTICLAMQHYGQSCL	1246
CACNA1D	KARP-------LRRYIPK--NPYQYKFWYV>V<NSSPFEYMMFVLIMLNTLCLAMQHYEQSKM	1252
CACNA1E	SAKP-------LTRYMPQNRHTFQYRVWHF>V<VSPSFEYTIMAMIALNTVVLMMKYYSAPCT	1505
CACNA1F	KAQP-------LRRYIPK--NPHQYRVWAT>V<NSAAFEYLMFLLILLNTVALAMQHYEQTAP	1217
CACNA1G	SGSSASAASEAQCKPYYSDYSRFRLLVHHL>C<TSHYLDLFITGVIGLNVVTMAMEHYQQPQI	1638
CACNA1H	EAQ---------RRPYYADYSPTRRSIHSL>C<TSHYLDLFITFIICVNVITMSMEHYNQPKS	1644
CACNA1I	KAQ---------RLPYYATYCHTRLLIHSM>C<TSHYLDIFITFIICLNVVTMSLEHYNQPTS	1514
CACNA1S	KARP-------LRCYIPK--NPYQYQVWYI>V<TSSYFEYLMFALIMLNTICLGMQHYNQSEQ	1145
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V1525M	c.4573G>A	Inherited Arrhythmia	BrS	rs199473269	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
		Inherited Arrhythmia	BrS	High prevalence of genetic variants previously associated with Brugada syndrome in new exome data. Clin Genet. 2013 23414114
		Inherited Arrhythmia	BrS	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