SCN5A Variant S524C

Summary of observed carriers, functional annotations, and structural context for SCN5A S524C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

22%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

S524C has not been reported 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 (%)
NA NA NA 0.511 29 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 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 S524C.
Neighbour residue Distance (Å) Observed variants
509 15
510 14
511 14
512 13 T512I,
513 13 R513C, c.1537delC, R513H, R513P,
514 12 G514C,
515 11
516 11
517 10 R517S, R517S,
518 9
519 8 S519F,
520 8 M520V, M520R,
521 7 K521E, c.1562delA,
522 5 P522S,
523 4 R523S, R523C, R523H,
524 0 c.1570_1571insG, S524Y,
525 4 S525G,
526 5 R526C, R526H,
527 7 G527R, G527R,
528 8 S528R, S528R, S528R,
529 8
530 9 F530V, F530S,
531 10 T531A, T531I,
532 11 F532L, F532C, F532L, F532L,
533 11 R533S, R533C, R533H,
534 12
535 13 R535G, R535X, R535Q,
536 13 D536H,
537 14
538 14 G538D
539 15