SCN5A Variant E428D

Summary of observed carriers, functional annotations, and structural context for SCN5A E428D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

E428D has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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	0.456	10	14

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 E428D.
Neighbour residue	Distance (Å)	Observed variants
413	15	A413T, A413E,
414	14	M414V,
415	14	A415T,
416	13	Y416C,
417	13
418	12	E418K,
419	11	Q419X,
420	11
421	10
422	9
423	8
424	8	I424M,
425	7	A425T, A425P
426	5
427	4
428	0	E428K,
429	4	E429K, p.E429del,
430	5	K430E,
431	7
432	8
433	8	R433C, R433H, R433S,
434	9
435	10
436	11
437	11	A437V,
438	12	M438L, M438T, M438L,
439	13	E439V, E439K,
440	13
441	14	L441F,
442	14
443	15