SCN5A Variant G452D

Summary of observed carriers, functional annotations, and structural context for SCN5A G452D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

10%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G452D 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 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 (%)
-2.79 0.997 -0.35 0.586 7 2

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 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 G452D.
Neighbour residue Distance (Å) Observed variants
437 15 A437V,
438 14 M438L, M438T, M438L,
439 14 E439K, E439V,
440 13
441 13 L441F,
442 12
443 11
444 11 E444fsX14,
445 10 H445Y, H445Q, H445Q, H445D,
446 9 E446K,
447 8 A447S, c.1339-24G>A, c.1338+2T>A, A447G,
448 8
449 7 T449A, Y449C,
450 5
451 4
452 0 G452D,
453 4 V453M,
454 5
455 7
456 8 V456M,
457 8
458 9 p.R458VfsX12, R458C, R458H,
459 10 S459G,
460 11
461 11 L461V,
462 12 E462A, E462K,
463 13 M463T, M463R,
464 13
465 14 p.P465LfsX5,
466 14 L466F, L466F,
467 15