SCN5A Variant R533S

Summary of observed carriers, functional annotations, and structural context for SCN5A R533S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/15 effective observations

Estimated BrS1 penetrance

6%

0/15 effective observations

Total carriers

5

0 BrS1 · 0 LQT3 · 5 unaffected

R533S is present in 5 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 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 (%)
-4.36 0.997 -2.07 0.708 2 7

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 – 5 5 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 R533S.
Neighbour residue Distance (Å) Observed variants
518 15
519 14 S519F,
520 14 M520V, M520R,
521 13 K521E, c.1562delA,
522 13 P522S,
523 12 R523H, R523C, R523S,
524 11 c.1570_1571insG, S524Y,
525 11 S525G,
526 10 R526C, R526H,
527 9 G527R, G527R,
528 8 S528R, S528R, S528R,
529 8
530 7 F530S, F530V,
531 5 T531A, T531I,
532 4 F532L, F532L, F532L, F532C,
533 0 R533H, R533S, R533C,
534 4
535 5 R535Q, R535G, R535X,
536 7 D536H,
537 8
538 8 G538D,
539 9
540 10
541 11
542 11
543 12 F543L, F543L, F543L
544 13
545 13
546 14
547 14
548 15