SCN5A Variant G874D

Summary of observed carriers, functional annotations, and structural context for SCN5A G874D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/12 effective observations

Estimated BrS1 penetrance

11%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

G874D is present in 2 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 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 (%)
-1.11 0.003 -0.13 0.663 12 0

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 – 2 2 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 G874D.
Neighbour residue Distance (Å) Observed variants
880 12
870 6
867 14 E867K, E867Q, E867X,
1440 13 W1440X,
864 14
871 5
909 12
876 7
868 10 c.2602delC, L868X,
882 15
872 6 D872N,
865 11
866 12 S866P, S866L,
874 0 G874D,
878 12 R878C, R878H, R878L,
350 14 H350Q, H350Q,
1441 15 E1441Q
877 8
879 15 W879R, W879R,
869 8 R869S, R869S,
905 12
875 4
908 11
873 4 S873A,