SCN5A Variant V453L

Summary of observed carriers, functional annotations, and structural context for SCN5A V453L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

7%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

V453L has not been reported 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 (%)
NA NA NA 0.242 4 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 – 0 0 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 V453L.
Neighbour residue Distance (Å) Observed variants
438 15 M438T, M438L, M438L,
439 14 E439V, E439K,
440 14
441 13 L441F
442 13
443 12
444 11 E444fsX14,
445 11 H445Q, H445Q, H445D, H445Y,
446 10 E446K,
447 9 c.1338+2T>A, A447G, A447S, c.1339-24G>A,
448 8
449 8 T449A, Y449C,
450 7
451 5
452 4 G452D,
453 0 V453M,
454 4
455 5
456 7 V456M,
457 8
458 8 R458C, p.R458VfsX12, R458H,
459 9 S459G,
460 10
461 11 L461V,
462 11 E462K, E462A,
463 12 M463T, M463R,
464 13
465 13 p.P465LfsX5,
466 14 L466F, L466F,
467 14
468 15 P468L,