SCN5A Variant P495L

Summary of observed carriers, functional annotations, and structural context for SCN5A P495L. 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

P495L 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	0.364	2	0

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 P495L.
Neighbour residue	Distance (Å)	Observed variants
480	15	K480N,
481	14	R481W, R481Q,
482	14	M482I,
483	13
484	13
485	12
486	11	T486S, T486A,
487	11
488	10
489	9
490	8	G490A, G490E,
491	8	E491G,
492	7
493	5	R493K,
494	4
495	0
496	4	K496M, K496N,
497	5	S497C,
498	7
499	8
500	8	E500K,
501	9	D501G,
502	10
503	11	P503S,
504	11	R504T,
505	12	A505E,
506	13	M506K,
507	13	p.N507_L515dup,
508	14
509	14
510	15