Paralogue Annotation for SCN5A residue 1501

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1501
Reference Amino Acid: L - Leucine
Protein Domain: Interdomain Linker III-IV

Paralogue Variants mapped to SCN5A residue 1501

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	L1514S	Dravet syndrome	Medium	2	20522430

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	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPLNKYQ	1518
SCN1A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPGNKFQ	1531
SCN2A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPANKFQ	1521
SCN3A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPANKFQ	1516
SCN4A	GGKDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPQNKIQ	1343
SCN7A	GGSNIFITVKQRKQY------RRL---KK->L<----M-YEDS--------QRPVPRPLNKLQ	1241
SCN8A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPLNKIQ	1512
SCN9A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPGNKIQ	1494
SCN10A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPLNKFQ	1466
SCN11A	GGQDIFMTEEQKKYY------NAM---KK->L<----G-SKKP--------QKPIPRPLNKCQ	1356
CACNA1A	----MEEYSLEKNER------ACI---DFA>I<------SAKP-------LTRHMPQNKQSFQ	1556
CACNA1B	----MSECSLEKNER------ACI---DFA>I<------SAKP-------LTRYMPQNRQSFQ	1462
CACNA1C	----YKNCELDKNQR------QCV---EYA>L<------KARP-------LRRYIPK--NQHQ	1209
CACNA1D	----YKNCELDKNQR------QCV---EYA>L<------KARP-------LRRYIPK--NPYQ	1215
CACNA1E	----MEECSLEKNER------ACI---DFA>I<------SAKP-------LTRYMPQNRHTFQ	1468
CACNA1F	----YQNCELDKNQR------QCV---EYA>L<------KAQP-------LRRYIPK--NPHQ	1180
CACNA1G	EEEEARRREEKRLRRLEKKRRNLML--DDV>I<-----ASGSSASAASEAQCKPYYSDYSRFR	1601
CACNA1H	EAEEARRREEK----------RLRRLERRR>R<STFPSPEAQ---------RRPYYADYSPTR	1607
CACNA1I	EAEEARRREEK----------RLRRLEKKR>R<------KAQ---------RLPYYATYCHTR	1477
CACNA1S	----YKNCELDKNQR------QCV---QYA>L<------KARP-------LRCYIPK--NPYQ	1108
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L1501V	c.4501C>G	Inherited Arrhythmia	LQTS,BrS	rs199473266	SIFT: deleterious Polyphen: benign
Reports		Inherited Arrhythmia	LQTS	Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849
		Inherited Arrhythmia	LQTS	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 Arrhythmia	LQTS	Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
		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	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
		Inherited Arrhythmia	LQTS	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