Paralogue Annotation for SCN5A residue 1486

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1486
Reference Amino Acid: F - Phenylalanine
Protein Domain: Interdomain Linker III-IV

Paralogue Variants mapped to SCN5A residue 1486

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	F1499L	Hemiplegic migraine 2	High	6	19332696
SCN9A	F1462V	Paroxysmal extreme pain disorder	High	6	17145499

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	FGSFFTLNLFIGVIIDNFNQQKKKLGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1502
SCN1A	FGSFFTLNLFIGVIIDNFNQQKKKFGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1515
SCN2A	FGSFFTLNLFIGVIIDNFNQQKKKFGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1505
SCN3A	FGSFFTLNLFIGVIIDNFNQQKKKFGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1500
SCN4A	FGSFFTLNLFIGVIIDNFNQQKKKLGGKDI>F<MTEEQKKYY------NAM---KK-L----G	1327
SCN7A	FGVFLPLSMLITVIIDNFNKHKIKLGGSNI>F<ITVKQRKQY------RRL---KK-L----M	1225
SCN8A	FGSFFTLNLFIGVIIDNFNQQKKKFGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1496
SCN9A	FGSFFTLNLFIGVIIDNFNQQKKKLGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1478
SCN10A	FGGFFTLNLFVGVIIDNFNQQKKKLGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1450
SCN11A	FGSFFTLNLFIGVIIDNFNQQQKKLGGQDI>F<MTEEQKKYY------NAM---KK-L----G	1340
CACNA1A	VFPFFFVNIFVALIIITFQEQGDKM----M>E<EYSLEKNER------ACI---DFAI-----	1539
CACNA1B	VFPFFFVNIFVALIIITFQEQGDKV----M>S<ECSLEKNER------ACI---DFAI-----	1445
CACNA1C	IIAFFMMNIFVGFVIVTFQEQGEQE----Y>K<NCELDKNQR------QCV---EYAL-----	1194
CACNA1D	IVAFFMMNIFVGFVIVTFQEQGEKE----Y>K<NCELDKNQR------QCV---EYAL-----	1200
CACNA1E	VFPFFFVNIFVALIIITFQEQGDKM----M>E<ECSLEKNER------ACI---DFAI-----	1451
CACNA1F	IIAFFMMNIFVGFVIITFRAQGEQE----Y>Q<NCELDKNQR------QCV---EYAL-----	1165
CACNA1G	IVAFFVLNMFVGVVVENFHKCRQHQEEEEA>R<RREEKRLRRLEKKRRNLML--DDVI-----	1576
CACNA1H	IVSFFVLNMFVGVVVENFHKCRQHQEAEEA>R<RREEK----------RLRRLERRRRSTFPS	1591
CACNA1I	IVSFFVLNMFVGVVVENFHKCRQHQEAEEA>R<RREEK----------RLRRLEKKRR-----	1462
CACNA1S	LIAFFMMNIFVGFVIVTFQEQGETE----Y>K<NCELDKNQR------QCV---QYAL-----	1093
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See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.F1486L	c.4456T>C	Other Cardiac Phenotype		rs199473615	SIFT: deleterious Polyphen: benign
Reports		Other Cardiac Phenotype		Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007 115(3):361-7. 17210839
		Other Cardiac Phenotype		Human voltage-gated sodium channel mutations that cause inherited neuronal and muscle channelopathies increase resurgent sodium currents. J Clin Invest. 2010 120(1):369-78. doi: 10.1172/JCI40801. 20038812
		Other Cardiac Phenotype		Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation. 2007 115(3):368-76. 17210841