SCN5A Variant H445P

Summary of observed carriers, functional annotations, and structural context for SCN5A H445P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/10 effective observations

Estimated BrS1 penetrance

14%

1/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

H445P has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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	0.645	12	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	14	0	1	–	–

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 H445P.
Neighbour residue	Distance (Å)	Observed variants
430	15	K430E,
431	14
432	14
433	13	R433C, R433H, R433S,
434	13
435	12
436	11
437	11	A437V,
438	10	M438L, M438T,
439	9	E439K, E439V,
440	8
441	8	L441F,
442	7
443	5
444	4	E444fsX14,
445	0	H445Q, H445Y, H445D,
446	4	E446K,
447	5	A447S, A447G, c.1338+2T>A, c.1339-24G>A
448	7
449	8	T449A, Y449C,
450	8
451	9
452	10	G452D,
453	11	V453M,
454	11
455	12
456	13	V456M,
457	13
458	14	p.R458VfsX12, R458C, R458H,
459	14	S459G,
460	15