Paralogue Annotation for SCN5A residue 846

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 846
Reference Amino Acid: L - Leucine
Protein Domain: TM Domain 2

Paralogue Variants mapped to SCN5A residue 846

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CACNA1A	L621R	Episodic ataxia	High	9	20156848
SCN1A	L897S	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	FKLAKSWPTLNTLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKNYSEL-RDS----	871
SCN1A	FKLAKSWPTLNMLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKSYKDC-VCK----	922
SCN2A	FKLAKSWPTLNMLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKSYKEC-VCK----	913
SCN3A	FKLAKSWPTLNMLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKSYKEC-VCK----	914
SCN4A	FKLAKSWPTLNMLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKSYKEC-VCK----	732
SCN7A	FKLGKYWPTFQILMWSLSNSWVALKDLVLL>L<FTFIFFSAAFGMKLFGKNYEEF-VCH----	659
SCN8A	FKLAKSWPTLNMLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKSYKEC-VCK----	907
SCN9A	FKLAKSWPTLNMLIKIIGNSVGALGNLTLV>L<AIIVFIFAVVGMQLFGKSYKEC-VCK----	887
SCN10A	FKLAKSWPTLNTLIKIIGNSVGALGNLTII>L<AIIVFVFALVGKQLLGENYRNN-RKN----	819
SCN11A	FKLAKSWPTLNTLIKIIGNSVGALGSLTVV>L<VIVIFIFSVVGMQLFGRSFNSQ-KSPKLCN	737
CACNA1A	FKVTKYWASLRNLVVSLLNSMKSIISLLFL>L<FLFIVVFALLGMQLFGGQFNFD-E------	644
CACNA1B	FKVTKYWSSLRNLVVSLLNSMKSIISLLFL>L<FLFIVVFALLGMQLFGGQFNFQ-D------	640
CACNA1C	FKITRYWNSLSNLVASLLNSVRSIASLLLL>L<FLFIIIFSLLGMQLFGGKFNFD-E------	681
CACNA1D	FKVTRHWTSLSNLVASLLNSMKSIASLLLL>L<FLFIIIFSLLGMQLFGGKFNFD-E------	700
CACNA1E	FKITKYWASLRNLVVSLMSSMKSIISLLFL>L<FLFIVVFALLGMQLFGGRFNFN-D------	633
CACNA1F	FKVTRHWASLSNLVASLLNSMKSIASLLLL>L<FLFIIIFSLLGMQLFGGKFNFD-Q------	686
CACNA1G	LKLVRFLPALQRQLVVLMKTMDNVATFCML>L<MLFIFIFSILGMHLFGCKFASER-------	895
CACNA1H	LKLVRFLPALRRQLVVLVKTMDNVATFCTL>L<MLFIFIFSILGMHLFGCKFSLKTD------	946
CACNA1I	LKLVRFMPALRRQLVVLMKTMDNVATFCML>L<MLFIFIFSILGMHIFGCKFSLRTD------	793
CACNA1S	FKITKYWTSLSNLVASLLNSIRSIASLLLL>L<FLFIVIFALLGMQLFGGRYDFE-D------	589
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L846R	c.2537T>G	Other Cardiac Phenotype			SIFT: deleterious Polyphen: probably damaging
Reports		Other Cardiac Phenotype		Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization. Circ Arrhythm Electrophysiol. 2011 4(6):874-81. 22028457