SCN5A Variant D372H

Summary of observed carriers, functional annotations, and structural context for SCN5A D372H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

26%

1/10 effective observations

Estimated BrS1 penetrance

29%

2/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

D372H has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 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	0.97	38	33

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	12	1	2	–	–

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 D372H.
Neighbour residue	Distance (Å)	Observed variants
364	9
891	14	I891T, I891N,
890	14	I890T,
919	12
901	9	E901K, S901L,
363	10
896	11	C896S,
895	12	L895F,
1417	13
396	13	V396L, V396A,
894	9	I894M,
355	15	F355C, F355I,
372	0
401	11	S401P,
926	15
371	6	Q371E,
1711	10	c.5131delG,
928	13	L928P,
361	14
904	11	W904X,
366	9
365	11
1706	12	Q1706H,
376	10	R376H, R376C,
897	6	G897R, G897E,
924	14	V924I,
927	12	N927S, N927K,
369	10	M369K,
1422	13	M1422R,
378	13
1418	11
902	10
402	14	F402L,
892	15	F892I,
349	13	D349N,
373	4
1712	12	G1712C, G1712S,
379	14
898	6
893	9	R893C, R893H,
922	13	V922I,
397	11	I397T, I397F, I397V,
405	13
362	14
261	15
920	12
1709	11	T1709R, T1709M, p.T1709del,
1420	13	G1420D, G1420P, G1420R, G1420V,
900	6
393	13
1713	14
916	14
1708	15	T1708I,
1421	12
374	8	W374G,
350	14	H350Q,
903	10	p.M903CfsX29,
367	4	R367L, R367C, R367H,
1760	15
370	6	T370M,
923	9
905	14
375	9
368	8
899	5
1710	11	S1710L,
380	14
377	9
400	14	G400R, G400A, G400E,
1419	10	K1419E,
353	12	T353I,
907	15