Paralogue Annotation for SCN5A residue 1378

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1378
Reference Amino Acid: V - Valine
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1378

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	V1390M	Myoclonic epilepsy of infancy	High	4	12083760, 22780858
SCN1A	V1390L	Generalised epilepsy with febrile seizures plus 2	High	4	21775168, 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	IMGVNLFAGKFGRCINQTEGDL-P-LNYTI>V<NNKSQCESLNLTGE--LYWTKVKVNFDNVG	1406
SCN1A	IMGVNLFAGKFYHCINTTTGDR---FDIED>V<NNHTDCLKLIERNET-ARWKNVKVNFDNVG	1419
SCN2A	IMGVNLFAGKFYHCINYTTGEM---FDVSV>V<NNYSECKALIESNQT-ARWKNVKVNFDNVG	1409
SCN3A	IMGVNLFAGKFYHCVNMTTGNM---FDISD>V<NNLSDCQALGK--Q--ARWKNVKVNFDNVG	1404
SCN4A	IMGVNLFAGKFYYCINTTTSER---FDISE>V<NNKSECESLMHTGQ--VRWLNVKVNYDNVG	1231
SCN7A	IMGVDLFAGRFYECIDPTSGER---FPSSE>V<MNKSRCESLLFNES--MLWENAKMNFDNVG	1129
SCN8A	IMGVNLFAGKYHYCFNETSEIR---FEIED>V<NNKTECEKLMEGNNTEIRWKNVKINFDNVG	1400
SCN9A	IMGVNLFAGKFYECINTTDGSR---FPASQ>V<PNRSECFALMNVSQN-VRWKNLKVNFDNVG	1382
SCN10A	IMGVNLFAGKFWRCINYTDGEF-SLVPLSI>V<NNKSDCKIQNSTGS--FFWVNVKVNFDNVA	1354
SCN11A	ILGVYFFSGKFGKCINGTDSVI----NYTI>I<TNKSQCESGN------FSWINQKVNFDNVG	1244
CACNA1A	VVAVQLFKGKFFHCTDESKEFEKDCRGKYL>L<YEKNEVK----AR--DREWKKYEFHYDNVL	1447
CACNA1B	VIAVQLFKGKFFYCTDESKELERDCRGQYL>D<YEKEEVE----AQ--PRQWKKYDFHYDNVL	1353
CACNA1C	CIGVQLFKGKLYTCSDSSKQTEAECKGNYI>T<YKDGEVDHP-IIQ--PRSWENSKFDFDNVL	1102
CACNA1D	CIGVQLFKGKFYRCTDEAKSNPEECRGLFI>L<YKDGDVDSP-VVR--ERIWQNSDFNFDNVL	1108
CACNA1E	VIAVQLFKGKFFYCTDSSKDTEKECIGNYV>D<HEKNKME----VK--GREWKRHEFHYDNII	1359
CACNA1F	CIGVQLFKGKFYTCTDEAKHTPQECKGSFL>V<YPDGDVSRP-LVR--ERLWVNSDFNFDNVL	1073
CACNA1G	ILGVQLFKGKFFVCQGED---------TRN>I<TNKSDCA----EA--SYRWVRHKYNFDNLG	1473
CACNA1H	ILGVQLFKGKFYYCEGPD---------TRN>I<STKAQCR----AA--HYRWVRRKYNFDNLG	1491
CACNA1I	ILGVQLFKGKFYHCLGVD---------TRN>I<TNRSDCM----AA--NYRWVHHKYNFDNLG	1367
CACNA1S	CIGVQLFKGKFFRCTDLSKMTEEECRGYYY>V<YKDGDPMQI-ELR--HREWVHSDFHFDNVL	1001
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V1378M	c.4132G>A	Inherited Arrhythmia	BrS		SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	BrS	Mexiletine differentially restores the trafficking defects caused by two brugada syndrome mutations. Front Pharmacol. 2012 3:62. 22529811