SCN5A Variant P465S

Summary of observed carriers, functional annotations, and structural context for SCN5A P465S. 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

P465S 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	0.396	3	4

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 P465S.
Neighbour residue	Distance (Å)	Observed variants
450	15
451	14
452	14	G452D,
453	13	V453M,
454	13
455	12
456	11	V456M,
457	11
458	10	p.R458VfsX12, R458C, R458H,
459	9	S459G,
460	8
461	8	L461V,
462	7	E462K, E462A,
463	5	M463R, M463T,
464	4
465	0	p.P465LfsX5,
466	4	L466F, L466F,
467	5
468	7	P468L,
469	8	V469I,
470	8	N470K, N470K,
471	9
472	10
473	11	E473X,
474	11	R474G, R474K,
475	12	R475S, R475K, R475S,
476	13
477	13	c.1428_1431delCAAG,
478	14
479	14
480	15	K480N, K480N,