SCN5A Variant E654D

Summary of observed carriers, functional annotations, and structural context for SCN5A E654D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

9%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E654D is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-1.01 0.79 -0.16 0.511 3 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 – 1 1 0 0 –
Variant features alone – 15 15 0 0 – –

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 E654D.
Neighbour residue Distance (Å) Observed variants
639 15 G639A, G639R, G639R,
640 14 P640A, P640L, P640S,
641 14
642 13
643 13
644 12
645 11
646 11 p.Q646RfsX5, c.1936delC,
647 10 A647S, A647D, A647V,
648 9 P648L,
649 8 C649Y, C649R,
650 8
651 7 c.1950_1953delAGAT, D651H,
652 5 G652D, G652S,
653 4
654 0 E654Q, E654D, E654K, E654X , E654D,
655 4 E655K,
656 5 P656L,
657 7
658 8 A658V,
659 8 R659W, R659Q,
660 9
661 10 R661W, R661Q,
662 11 c.1983_1993dupGGCCCTCAGCG, A662S,
663 11
664 12 S664G,
665 13 A665S, A665T,
666 13
667 14
668 14 V668I,
669 15