Paralogue Annotation for SCN5A residue 1768

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1768
Reference Amino Acid: I - Isoleucine
Protein Domain: TM Domain 4

Paralogue Variants mapped to SCN5A residue 1768

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	I1782S	Dravet syndrome	High	9	18930999
SCN1A	I1782M	Dravet syndrome	High	9	18930999, 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	D---CGSPAVGILFFTTYIIISFLIVVNMY>I<AIILENFSVATEESTEPLSEDDFDMFYEIW	1798
SCN1A	D---CGNPSVGIFFFVSYIIISFLVVVNMY>I<AVILENFSVATEESAEPLSEDDFEMFYEVW	1812
SCN2A	D---CGNPSVGIFFFVSYIIISFLVVVNMY>I<AVILENFSVATEESAEPLSEDDFEMFYEVW	1802
SCN3A	D---CGNPSVGIFFFVSYIIISFLVVVNMY>I<AVILENFSVATEESAEPLSEDDFEMFYEVW	1797
SCN4A	D---CGNPSIGICFFCSYIIISFLIVVNMY>I<AIILENFNVATEESSEPLGEDDFEMFYETW	1624
SCN7A	D---CGNPSVGIFYFVSYILISWLIIVNMY>I<VVVMEFLNIASKKKNKTLSEDDFRKFFQVW	1522
SCN8A	D---CGNPSVGIFFFVSYIIISFLIVVNMY>I<AIILENFSVATEESADPLSEDDFETFYEIW	1792
SCN9A	D---CGNPSVGIFYFVSYIIISFLVVVNMY>I<AVILENFSVATEESTEPLSEDDFEMFYEVW	1775
SCN10A	D---CGSPAVGIIFFTTYIIISFLIMVNMY>I<AVILENFNVATEESTEPLSEDDFDMFYETW	1748
SCN11A	N---CHLPGIATSYFVSYIIISFLIVVNMY>I<AVILENFNTATEESEDPLGEDDFDIFYEVW	1630
CACNA1A	R--ECGN-EFAYFYFVSFIFLCSFLMLNLF>V<AVIMDNFEYLTRDSSI-LGPHHLDEYVRVW	1836
CACNA1B	NATECGS-DFAYFYFVSFIFLCSFLMLNLF>V<AVIMDNFEYLTRDSSI-LGPHHLDEFIRVW	1734
CACNA1C	TP--CGS-SFAVFYFISFYMLCAFLIINLF>V<AVIMDNFDYLTRDWSI-LGPHHLDEFKRIW	1501
CACNA1D	YT--CGS-NFAIVYFISFYMLCAFLIINLF>V<AVIMDNFDYLTRDWSI-LGPHHLDEFKRIW	1509
CACNA1E	E--RCGT-DLAYVYFVSFIFFCSFLMLNLF>V<AVIMDNFEYLTRDSSI-LGPHHLDEFVRVW	1748
CACNA1F	FT--CGS-NFAIAYFISFFMLCAFLIINLF>V<AVIMDNFDYLTRDWSI-LGPHHLDEFKRIW	1466
CACNA1G	----YNT-VISPIYFVSFVLTAQFVLVNVV>I<AVLMKHLEESNKEAKE---EAELEAELELE	1874
CACNA1H	LS--YLP-ALSPVYFVTFVLVAQFVLVNVV>V<AVLMKHLEESNKEARE---DAELDAEIELE	1883
CACNA1I	LS--SLQ-FVSPLYFVSFVLTAQFVLINVV>V<AVLMKHLDDSNKEAQE---DAEMDAELELE	1753
CACNA1S	YT--CGT-NFAYYYFISFYMLCAFLVINLF>V<AVIMDNFDYLTRDWSI-LGPHHLDEFKAIW	1406
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.I1768V	c.5302A>G	Inherited Arrhythmia	LQTS	rs199473311	SIFT: deleterious Polyphen: possibly damaging
Reports		Inherited Arrhythmia	LQTS	A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics and channel dysfunction. Physiol Genomics. 2002 10(3):191-7. 12209021
		Inherited Arrhythmia	LQTS	The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome. J Med Genet. 2003 40(2):141-5. 12566525
		Inherited Arrhythmia	LQTS	Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336
		Inherited Arrhythmia	LQTS	Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
		Inherited Arrhythmia	LQTS	Cardiac channelopathy causing sudden death as revealed by molecular autopsy. Int J Legal Med. 2012 22370996
		Inherited Arrhythmia	LQTS	Mortality of inherited arrhythmia syndromes: insight into their natural history. Circ Cardiovasc Genet. 2012 5(2):183-9. 22373669
		Inherited Arrhythmia	LQTS	A novel LQT3 mutation implicates the human cardiac sodium channel domain IVS6 in inactivation kinetics. Cardiovasc Res. 2003 57(4):1072-8. 12650885
		Inherited Arrhythmia	LQTS	Follow up of a family with asymptomatic compound long QT syndrome mutations. Genet Couns. 2014 25(4):399-403. 25804018