SCN5A Variant S459C

Summary of observed carriers, functional annotations, and structural context for SCN5A S459C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/10 effective observations

Estimated BrS1 penetrance

7%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

S459C 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 0.659 1 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 – 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 S459C.
Neighbour residue Distance (Å) Observed variants
444 15 E444fsX14,
445 14 H445D, H445Y, H445Q, H445Q,
446 14 E446K,
447 13 c.1338+2T>A, c.1339-24G>A, A447S, A447G,
448 13
449 12 T449A, Y449C,
450 11
451 11
452 10 G452D,
453 9 V453M,
454 8
455 8
456 7 V456M,
457 5
458 4 p.R458VfsX12, R458C, R458H,
459 0 S459G,
460 4
461 5 L461V,
462 7 E462K, E462A,
463 8 M463T, M463R,
464 8
465 9 p.P465LfsX5,
466 10 L466F, L466F,
467 11
468 11 P468L,
469 12 V469I,
470 13 N470K, N470K,
471 13
472 14
473 14 E473X,
474 15 R474G, R474K