Paralogue Annotation for SCN5A residue 896

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 896
Reference Amino Acid: C - Cysteine
Protein Domain: TM Domain 2

Paralogue Variants mapped to SCN5A residue 896

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	C949Y	Dravet syndrome	High	9	18930999
SCN1A	C949S	Dravet syndrome	High	9	18930999
CACNA1A	T666M	Hemiplegic migraine and episodic ataxia 2	Medium	9	8898206, 10024348, 22000314, 22190617, 9488686, 22969264, 25266619, 25274239, 25274239, 22136990, 24270521, 24498617, 11971066, 11814735
SCN4A	C759S	Myotonia	High	9	22094069

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	--D-SG---LLPRWHMMDFFHAFLIIFRIL>C<GE-WIETMWDCMEV-----SGQSLCLLVFL	920
SCN1A	--I-AS-DCQLPRWHMNDFFHSFLIVFRVL>C<GE-WIETMWDCMEV-----AGQAMCLTVFM	973
SCN2A	--I-SN-DCELPRWHMHDFFHSFLIVFRVL>C<GE-WIETMWDCMEV-----AGQTMCLTVFM	964
SCN3A	--I-ND-DCTLPRWHMNDFFHSFLIVFRVL>C<GE-WIETMWDCMEV-----AGQTMCLIVFM	965
SCN4A	--I-AL-DCNLPRWHMHDFFHSFLIVFRIL>C<GE-WIETMWDCMEV-----AGQAMCLTVFL	783
SCN7A	--I-DK-DCQLPRWHMHDFFHSFLNVFRIL>C<GE-WVETLWDCMEV-----AGQSWCIPFYL	710
SCN8A	--I-NQ-DCELPRWHMHDFFHSFLIVFRVL>C<GE-WIETMWDCMEV-----AGQAMCLIVFM	958
SCN9A	--I-ND-DCTLPRWHMNDFFHSFLIVFRVL>C<GE-WIETMWDCMEV-----AGQAMCLIVYM	938
SCN10A	--I-SAPHEDWPRWHMHDFFHSFLIVFRIL>C<GE-WIENMWACMEV-----GQKSICLILFL	871
SCN11A	CNPTGPTVSCLRHWHMGDFWHSFLVVFRIL>C<GE-WIENMWECMQEAN---ASSSLCVIVFI	792
CACNA1A	--------G-TPPTNFDTFPAAIMTVFQIL>T<GEDWNEVMYDGIKSQGGV-QGGMVFSIYFI	695
CACNA1B	--------E-TPTTNFDTFPAAILTVFQIL>T<GEDWNAVMYHGIESQGGV-SKGMFSSFYFI	691
CACNA1C	--------MQTRRSTFDNFPQSLLTVFQIL>T<GEDWNSVMYDGIMAYGGPSFPGMLVCIYFI	734
CACNA1D	--------TQTKRSTFDNFPQALLTVFQIL>T<GEDWNAVMYDGIMAYGGPSSSGMIVCIYFI	753
CACNA1E	--------G-TPSANFDTFPAAIMTVFQIL>T<GEDWNEVMYNGIRSQGGV-SSGMWSAIYFI	684
CACNA1F	--------THTKRSTFDTFPQALLTVFQIL>T<GEDWNVVMYDGIMAYGGPFFPGMLVCIYFI	739
CACNA1G	----DG-DTLPDRKNFDSLLWAIVTVFQIL>T<QEDWNKVLYNGMAS-T-S----SWAALYFI	945
CACNA1H	----TG-DTVPDRKNFDSLLWAIVTVFQIL>T<QEDWNVVLYNGMAS-T-S----SWAALYFV	996
CACNA1I	----TG-DTVPDRKNFDSLLWAIVTVFQIL>T<QEDWNVVLYNGMAS-T-S----PWASLYFV	843
CACNA1S	--------TEVRRSNFDNFPQALISVFQVL>T<GEDWTSMMYNGIMAYGGPSYPGMLVCIYFI	642
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.C896S	c.2686T>A	Inherited Arrhythmia	BrS	rs199473173	SIFT: deleterious Polyphen: benign
Reports		Inherited Arrhythmia	BrS	Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002 105(11):1342-7. 11901046