SCN5A Variant R954G

Summary of observed carriers, functional annotations, and structural context for SCN5A R954G. 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

R954G 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 (%)
3.68	0	0.88	0.291	3	1

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 R954G.
Neighbour residue	Distance (Å)	Observed variants
939	15	L939F,
940	14	S940N,
941	14	S941F, S941N,
942	13
943	13	S943N,
944	12
945	11	D945G
946	11
947	10
948	9
949	8
950	8	P950X,
951	7	D951X, c.2850delT,
952	5	E952K,
953	4	D953E, D953E, D953Y,
954	0	R954G,
955	4	p.E955DfsX74,
956	5	M956I, M956I, M956I, M956T,
957	7
958	8
959	8	L959P,
960	9	Q960K,
961	10
962	11
963	11
964	12	A964G,
965	13	R965H, R965L, R965C,
966	13
967	14	Q967R,
968	14
969	15	G969S, G969C,