Paralogue Annotation for SCN5A residue 1767

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1767
Reference Amino Acid: Y - Tyrosine
Protein Domain: TM Domain 4

Paralogue Variants mapped to SCN5A residue 1767

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	Y1781H	Dravet syndrome	High	9	18930999
SCN1A	Y1781C	Myoclonic epilepsy of infancy	High	9	14738421, 23195492

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	GD---CGSPAVGILFFTTYIIISFLIVVNM>Y<IAIILENFSVATEESTEPLSEDDFDMFYEI	1797
SCN1A	GD---CGNPSVGIFFFVSYIIISFLVVVNM>Y<IAVILENFSVATEESAEPLSEDDFEMFYEV	1811
SCN2A	GD---CGNPSVGIFFFVSYIIISFLVVVNM>Y<IAVILENFSVATEESAEPLSEDDFEMFYEV	1801
SCN3A	GD---CGNPSVGIFFFVSYIIISFLVVVNM>Y<IAVILENFSVATEESAEPLSEDDFEMFYEV	1796
SCN4A	GD---CGNPSIGICFFCSYIIISFLIVVNM>Y<IAIILENFNVATEESSEPLGEDDFEMFYET	1623
SCN7A	GD---CGNPSVGIFYFVSYILISWLIIVNM>Y<IVVVMEFLNIASKKKNKTLSEDDFRKFFQV	1521
SCN8A	GD---CGNPSVGIFFFVSYIIISFLIVVNM>Y<IAIILENFSVATEESADPLSEDDFETFYEI	1791
SCN9A	GD---CGNPSVGIFYFVSYIIISFLVVVNM>Y<IAVILENFSVATEESTEPLSEDDFEMFYEV	1774
SCN10A	GD---CGSPAVGIIFFTTYIIISFLIMVNM>Y<IAVILENFNVATEESTEPLSEDDFDMFYET	1747
SCN11A	EN---CHLPGIATSYFVSYIIISFLIVVNM>Y<IAVILENFNTATEESEDPLGEDDFDIFYEV	1629
CACNA1A	-R--ECGN-EFAYFYFVSFIFLCSFLMLNL>F<VAVIMDNFEYLTRDSSI-LGPHHLDEYVRV	1835
CACNA1B	-NATECGS-DFAYFYFVSFIFLCSFLMLNL>F<VAVIMDNFEYLTRDSSI-LGPHHLDEFIRV	1733
CACNA1C	ETP--CGS-SFAVFYFISFYMLCAFLIINL>F<VAVIMDNFDYLTRDWSI-LGPHHLDEFKRI	1500
CACNA1D	EYT--CGS-NFAIVYFISFYMLCAFLIINL>F<VAVIMDNFDYLTRDWSI-LGPHHLDEFKRI	1508
CACNA1E	-E--RCGT-DLAYVYFVSFIFFCSFLMLNL>F<VAVIMDNFEYLTRDSSI-LGPHHLDEFVRV	1747
CACNA1F	EFT--CGS-NFAIAYFISFFMLCAFLIINL>F<VAVIMDNFDYLTRDWSI-LGPHHLDEFKRI	1465
CACNA1G	-----YNT-VISPIYFVSFVLTAQFVLVNV>V<IAVLMKHLEESNKEAKE---EAELEAELEL	1873
CACNA1H	-LS--YLP-ALSPVYFVTFVLVAQFVLVNV>V<VAVLMKHLEESNKEARE---DAELDAEIEL	1882
CACNA1I	-LS--SLQ-FVSPLYFVSFVLTAQFVLINV>V<VAVLMKHLDDSNKEAQE---DAEMDAELEL	1752
CACNA1S	EYT--CGT-NFAYYYFISFYMLCAFLVINL>F<VAVIMDNFDYLTRDWSI-LGPHHLDEFKAI	1405
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.Y1767C	c.5300A>G	Inherited Arrhythmia	LQTS	rs199473632	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944
Reports		Inherited Arrhythmia	LQTS	Y1767C, a novel SCN5A mutation, induces a persistent Na+ current and potentiates ranolazine inhibition of Nav1.5 channels. Am J Physiol Heart Circ Physiol. 2011 300(1):H288-99. 21076026