SCN5A Variant S457F

Summary of observed carriers, functional annotations, and structural context for SCN5A S457F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/10 effective observations

Estimated BrS1 penetrance

0/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

S457F has not been reported 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 (%)
NA	NA	NA	0.809	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	–	0	0	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 S457F.
Neighbour residue	Distance (Å)	Observed variants
442	15
443	14
444	14	E444fsX14,
445	13	H445D, H445Q, H445Y,
446	13	E446K,
447	12	A447S, c.1339-24G>A, c.1338+2T>A, A447G,
448	11
449	11	T449A, Y449C,
450	10
451	9
452	8	G452D,
453	8	V453M,
454	7
455	5
456	4	V456M,
457	0
458	4	R458C, R458H, p.R458VfsX12,
459	5	S459G,
460	7
461	8	L461V,
462	8	E462K, E462A,
463	9	M463R, M463T,
464	10
465	11	p.P465LfsX5,
466	11	L466F,
467	12
468	13	P468L,
469	13	V469I,
470	14	N470K,
471	14
472	15