SCN5A Variant M956I

Summary of observed carriers, functional annotations, and structural context for SCN5A M956I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/11 effective observations

Estimated BrS1 penetrance

0/11 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 1 unaffected

M956I is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density BrS (%)	Penetrance Density LQT3 (%)
-2.38	0.514	-0.71	0.571	1	3

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source	Year	Carriers	Unaffected	LQT3	BrS1	Other	Other Disease
Literature, cohort, and gnomAD	–	1	1	0	0		–
Variant features alone	–	15	15	0	0	–	–

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near M956I.
Neighbour residue	Distance (Å)	Observed variants
941	15	S941F, S941N,
942	14
943	14	S943N,
944	13
945	13	D945G,
946	12
947	11
948	11
949	10
950	9	P950X,
951	8	D951X, c.2850delT,
952	8	E952K,
953	7	D953E, D953Y, D953E,
954	5	R954G,
955	4	p.E955DfsX74,
956	0	M956I, M956I, M956I, M956T,
957	4
958	5
959	7	L959P,
960	8	Q960K,
961	8
962	9
963	10
964	11	A964G,
965	11	R965C, R965H, R965L,
966	12
967	13	Q967R,
968	13
969	14	G969C, G969S,
970	14
971	15	R971C, R971H,