SCN5A Variant E625D

Summary of observed carriers, functional annotations, and structural context for SCN5A E625D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/14 effective observations

Estimated BrS1 penetrance

15%

2/14 effective observations

Total carriers

4

0 BrS1 · 0 LQT3 · 4 unaffected

E625D is present in 4 alleles 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 2 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 (%)
-0.49 0 0.94 0.572 27 3

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 – 4 4 0 0 –
Variant features alone – 15 13 0 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 E625D.
Neighbour residue Distance (Å) Observed variants
610 15 E610K,
611 14
612 14
613 13
614 13 P614S,
615 12 G615E,
616 11 S616N,
617 11
618 10 L618F,
619 9 L619F,
620 8 R620C, R620H,
621 8
622 7
623 5 M623T,
624 4 L624Q,
625 0 E625D, E625Q, c.1872dupA, E625D,
626 4
627 5 P627L,
628 7 P628R,
629 8 D629Y,
630 8 T630M,
631 9 p.T631VfsX101, c.1890+5G>A, c.1890G>A,
632 10 T632M,
633 11
634 11 S634L, S634W,
635 12
636 13 E636K,
637 13 P637L,
638 14 G638D,
639 14 G639R, G639A, G639R
640 15 P640L, P640A, P640S,