Paralogue Annotation for SCN5A residue 717

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 717
Reference Amino Acid: P - Proline
Protein Domain: TM Domain 2

Paralogue Variants mapped to SCN5A residue 717

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	P768L	Myoclonic epilepsy of infancy	High	8	19350499, 24168886

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	NR-LAQRYLIWECCPLWMSIKQGVKLVVMD>P<FTDLTITMCIVLNTLFMALEHYNMTSEFEE	747
SCN1A	YK-FSNIFLIWDCSPYWLKVKHVVNLVVMD>P<FVDLAITICIVLNTLFMAMEHYPMTDHFNN	798
SCN2A	YK-FANMCLIWDCCKPWLKVKHLVNLVVMD>P<FVDLAITICIVLNTLFMAMEHYPMTEQFSS	789
SCN3A	YR-FANVFLIWDCCDAWLKVKHLVNLIVMD>P<FVDLAITICIVLNTLFMAMEHYPMTEQFSS	790
SCN4A	YK-CAHKVLIWNCCAPWLKFKNIIHLIVMD>P<FVDLGITICIVLNTLFMAMEHYPMTEHFDN	608
SCN7A	YK-FAKTFLIWNCSPCWLKLKEFVHRIIMA>P<FTDLFLIICIILNVCFLTLEHYPMSKQTNT	535
SCN8A	YK-FANTFLIWECHPYWIKLKEIVNLIVMD>P<FVDLAITICIVLNTLFMAMEHHPMTPQFEH	783
SCN9A	YR-FAHKFLIWNCSPYWIKFKKCIYFIVMD>P<FVDLAITICIVLNTLFMAMEHHPMTEEFKN	763
SCN10A	TS-LSQKYLIWDCCPMWVKLKTILFGLVTD>P<FAELTITLCIVVNTIFMAMEHHGMSPTFEA	695
SCN11A	EN-LASKYLVWNCCPQWLCVKKVLRTVMTD>P<FTELAITICIIINTVFLAMEHHKMEASFEK	607
CACNA1A	IK-SAKLENSTFFHKKERRMRFYIRRMVKT>Q<AFYWTVLSLVALNTLCVAIVHYNQPEWLSD	517
CACNA1B	LK-SGKTESSSYFRRKEKMFRFFIRRMVKA>Q<SFYWVVLCVVALNTLCVAMVHYNQPRRLTT	513
CACNA1C	HR-ISKSKFSRYWRRWNRFCRRKCRAAVKS>N<VFYWLVIFLVFLNTLTIASEHYNQPNWLTE	554
CACNA1D	QA-ISKSKLSRRWRRWNRFNRRRCRAAVKS>V<TFYWLVIVLVFLNTLTISSEHYNQPDWLTQ	573
CACNA1E	IK-SAKVDGVSYFRHKERLLRISIRHMVKS>Q<VFYWIVLSLVALNTACVAIVHHNQPQWLTH	506
CACNA1F	NK-IMKTRVCRRLRRANRVLRARCRRAVKS>N<ACYWAVLLLVFLNTLTIASEHHGQPVWLTQ	559
CACNA1G	--SLGPDAEPSSVLAFWRLICDTFRKIVDS>K<YFGRGIMIAILVNTLSMGIEYHEQPEELTN	773
CACNA1H	QQRAAPGE-PGWMGRLWVTFSGKLRRIVDS>K<YFSRGIMMAILVNTLSMGVEYHEQPEELTN	823
CACNA1I	EE-QADGA-VWLCGDVWRETRAKLRGIVDS>K<YFNRGIMMAILVNTVSMGIEHHEQPEELTN	670
CACNA1S	NK-I--IQFIRHWRQWNRIFRWKCHDIVKS>K<VFYWLVILIVALNTLSIASEHHNQPLWLTR	462
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.P717L	c.2150C>T	Inherited Arrhythmia	BrS	rs199473149	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