SCN5A Variant S464P

Summary of observed carriers, functional annotations, and structural context for SCN5A S464P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

10%

0/10 effective observations

Estimated BrS1 penetrance

0/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

S464P 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	0.754	2	10

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 S464P.
Neighbour residue	Distance (Å)	Observed variants
449	15	T449A, Y449C
450	14
451	14
452	13	G452D,
453	13	V453M,
454	12
455	11
456	11	V456M,
457	10
458	9	p.R458VfsX12, R458H, R458C,
459	8	S459G,
460	8
461	7	L461V,
462	5	E462K, E462A,
463	4	M463T, M463R,
464	0
465	4	p.P465LfsX5,
466	5	L466F,
467	7
468	8	P468L,
469	8	V469I,
470	9	N470K,
471	10
472	11
473	11	E473X,
474	12	R474K, R474G,
475	13	R475K, R475S,
476	13
477	14	c.1428_1431delCAAG,
478	14
479	15