SCN5A Variant D651H

Summary of observed carriers, functional annotations, and structural context for SCN5A D651H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

23%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

D651H is present in 1 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 (%)
-3.85 0.918 0.4 0.683 32 1

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 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 D651H.
Neighbour residue Distance (Å) Observed variants
636 15 E636K,
637 14 P637L,
638 14 G638D,
639 13 G639R, G639A, G639R
640 13 P640L, P640A, P640S,
641 12
642 11
643 11
644 10
645 9
646 8 c.1936delC, p.Q646RfsX5,
647 8 A647S, A647D, A647V,
648 7 P648L,
649 5 C649R, C649Y,
650 4
651 0 c.1950_1953delAGAT, D651H,
652 4 G652D, G652S,
653 5
654 7 E654D, E654K, E654Q, E654X , E654D,
655 8 E655K,
656 8 P656L,
657 9
658 10 A658V,
659 11 R659W, R659Q,
660 11
661 12 R661Q, R661W,
662 13 c.1983_1993dupGGCCCTCAGCG, A662S,
663 13
664 14 S664G,
665 14 A665S, A665T,
666 15