Paralogue Annotation for SCN5A residue 1323

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1323
Reference Amino Acid: V - Valine
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1323

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN9A	V1299F	Paroxysmal extreme pain disorder	High	9	17145499, 18599537, 21115638
SCN2A	V1326D	Migrating focal seizures of infancy	High	9	23988467
SCN2A	V1326L	Ohtahara syndrome	High	9	23935176
SCN4A	V1149L	Episodic paralyses and myotonic discharges	High	9	25724373

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	FAEMGPIKSLRTLRALRPLRALSRFEGMRV>V<VNALVGAIPSIMNVLLVCLIFWLIFSIMGV	1353
SCN1A	YSELGAIKSLRTLRALRPLRALSRFEGMRV>V<VNALLGAIPSIMNVLLVCLIFWLIFSIMGV	1366
SCN2A	YSELGAIKSLRTLRALRPLRALSRFEGMRV>V<VNALLGAIPSIMNVLLVCLIFWLIFSIMGV	1356
SCN3A	YSELGAIKSLRTLRALRPLRALSRFEGMRV>V<VNALVGAIPSIMNVLLVCLIFWLIFSIMGV	1354
SCN4A	YSELGPIKSLRTLRALRPLRALSRFEGMRV>V<VNALLGAIPSIMNVLLVCLIFWLIFSIMGV	1179
SCN7A	--E---LKPLISMKFLRPLRVLSQFERMKV>V<VRALIKTTLPTLNVFLVCLMIWLIFSIMGV	1077
SCN8A	YSELGAIKSLRTLRALRPLRALSRFEGMRV>V<VNALVGAIPSIMNVLLVCLIFWLIFSIMGV	1346
SCN9A	YSDLGPIKSLRTLRALRPLRALSRFEGMRV>V<VNALIGAIPSIMNVLLVCLIFWLIFSIMGV	1329
SCN10A	YSEVAPIKALRTLRALRPLRALSRFEGMRV>V<VDALVGAIPSIMNVLLVCLIFWLIFSIMGV	1300
SCN11A	---LMELKSFRTLRALRPLRALSQFEGMKV>V<VNALIGAIPAILNVLLVCLIFWLVFCILGV	1197
CACNA1A	GKDINTIKSLRVLRVLRPLKTIKRLPKLKA>V<FDCVVNSLKNVFNILIVYMLFMFIFAVVAV	1396
CACNA1B	GKDINTIKSLRVLRVLRPLKTIKRLPKLKA>V<FDCVVNSLKNVLNILIVYMLFMFIFAVIAV	1302
CACNA1C	SSAINVVKILRVLRVLRPLRAINRAKGLKH>V<VQCVFVAIRTIGNIVIVTTLLQFMFACIGV	1048
CACNA1D	SSAISVVKILRVLRVLRPLRAINRAKGLKH>V<VQCVFVAIRTIGNIMIVTTLLQFMFACIGV	1054
CACNA1E	GRDIKTIKSLRVLRVLRPLKTIKRLPKLKA>V<FDCVVTSLKNVFNILIVYKLFMFIFAVIAV	1308
CACNA1F	SSAISVVKILRVLRVLRPLRAINRAKGLKH>V<VQCVFVAIRTIGNIMIVTTLLQFMFACIGV	1019
CACNA1G	TKILGMLRVLRLLRTLRPLRVISRAQGLKL>V<VETLMSSLKPIGNIVVICCAFFIIFGILGV	1431
CACNA1H	AKILGVLRVLRLLRTLRPLRVISRAPGLKL>V<VETLISSLRPIGNIVLICCAFFIIFGILGV	1449
CACNA1I	AKILGVLRVLRLLRTLRPLRVISRAPGLKL>V<VETLISSLKPIGNIVLICCAFFIIFGILGV	1325
CACNA1S	SSAISVVKILRVLRVLRPLRAINRAKGLKH>V<VQCMFVAISTIGNIVLVTTLLQFMFACIGV	947
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V1323G	c.3968T>G	Inherited Arrhythmia	BrS	rs199473221	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	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