Paralogue Annotation for SCN5A residue 1208

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1208
Reference Amino Acid: E - Glutamate
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1208

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN2A	E1211K	Neonatal-infantile seizures	High	9	19786696, 25459969
SCN1A	E1221K	Dravet syndrome C ?	High	9	21248271
SCN1A	E1221Q	Dravet syndrome	High	9	26096185

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	VDTTQAP---GKVWWRLRKTCYHIVEHSWF>E<TFIIFMILLSSGALAFEDIYLEERKTIKVL	1238
SCN1A	INVEEGR---GKQWWNLRRTCFRIVEHNWF>E<TFIVFMILLSSGALAFEDIYIDQRKTIKTM	1251
SCN2A	ISIEEGK---GKLWWNLRKTCYKIVEHNWF>E<TFIVFMILLSSGALAFEDIYIEQRKTIKTM	1241
SCN3A	VSTEEGK---GKIWWNLRKTCYSIVEHNWF>E<TFIVFMILLSSGALAFEDIYIEQRKTIKTM	1239
SCN4A	VDISQGR---GKKWWTLRRACFKIVEHNWF>E<TFIVFMILLSSGALAFEDIYIEQRRVIRTI	1064
SCN7A	ISGASKK---GKIWQNIRKTCCKIVENNWF>K<CFIGLVTLLSTGTLAFEDIYMDQRKTIKIL	967
SCN8A	VNIEEGL---GKSWWILRKTCFLIVEHNWF>E<TFIIFMILLSSGALAFEDIYIEQRKTIRTI	1231
SCN9A	VNIESGK---GKIWWNIRKTCYKIVEHSWF>E<SFIVLMILLSSGALAFEDIYIERKKTIKII	1214
SCN10A	LDTTKSP---WDVGWQVRKTCYRIVEHSWF>E<SFIIFMILLSSGSLAFEDYYLDQKPTVKAL	1185
SCN11A	VDKRKPP---WVIWWNLRKTCYQIVKHSWF>E<SFIIFVILLSSGALIFEDVHLENQPKIQEL	1089
CACNA1A	PMPPYSSMFILSTTNPLRRLCHYILNLRYF>E<MCILMVIAMSSIALAAEDPV-QPNAPRNNV	1276
CACNA1B	PIVPYSSMFCLSPTNLLRRFCHYIVTMRYF>E<VVILVVIALSSIALAAEDPV-RTDSPRNNA	1183
CACNA1C	PMPEASAFFIFSSNNRFRLQCHRIVNDTIF>T<NLILFFILLSSISLAAEDPV-QHTSFRNHI	932
CACNA1D	PIPEGSAFFILSKTNPIRVGCHKLINHHIF>T<NLILVFIMLSSAALAAEDPI-RSHSFRNTI	938
CACNA1E	AMVPHSSMFIFSTTNPIRRACHYIVNLRYF>E<MCILLVIAASSIALAAEDPV-LTNSERNKV	1185
CACNA1F	PIPEGSAFFCLSQTNPLRKGCHTLIHHHVF>T<NLILVFIILSSVSLAAEDPI-RAHSFRNHI	903
CACNA1G	ERDSWSAY-IFPPQSRFRLLCHRIITHKMF>D<HVVLVIIFLNCITIAMERPKIDPHSAERIF	1309
CACNA1H	SREAWALY-LFSPQNRFRVSCQKVITHKMF>D<HVVLVFIFLNCVTIALERPDIDPGSTERVF	1327
CACNA1I	VREDWSVY-LFSPENRFRVLCQTIIAHKLF>D<YVVLAFIFLNCITIALERPQIEAGSTERIF	1203
CACNA1S	PIPEASSFFIFSPTNKIRVLCHRIVNATWF>T<NFILLFILLSSAALAAEDPI-RADSMRNQI	831
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.E1208K	c.3622G>A	Inherited Arrhythmia			SIFT: Polyphen:
Reports		Inherited Arrhythmia	BrS	Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel. Circ Cardiovasc Genet. 2015 8(4):582-95. doi: 10.1161/CIRCGENETICS.114.000831. 25904541