SCN5A Variant E426Q

Summary of observed carriers, functional annotations, and structural context for SCN5A E426Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

23%

1/10 effective observations

Estimated BrS1 penetrance

10%

1/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

E426Q 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 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	0.737	6	29

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	13	1	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 E426Q.
Neighbour residue	Distance (Å)	Observed variants
411	15	V411M,
412	14	V412D,
413	14	A413T, A413E,
414	13	M414V,
415	13	A415T,
416	12	Y416C,
417	11
418	11	E418K,
419	10	Q419X
420	9
421	8
422	8
423	7
424	5	I424M,
425	4	A425T, A425P,
426	0
427	4
428	5	E428K,
429	7	p.E429del, E429K,
430	8	K430E,
431	8
432	9
433	10	R433H, R433C, R433S,
434	11
435	11
436	12
437	13	A437V,
438	13	M438L, M438L, M438T,
439	14	E439K, E439V,
440	14
441	15	L441F,