SCN5A Variant P503S

Summary of observed carriers, functional annotations, and structural context for SCN5A P503S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

8%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

P503S 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 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 (%)
-0.01 0.992 -0.2 0.324 8 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 – 1 1 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 P503S.
Neighbour residue Distance (Å) Observed variants
488 15
489 14
490 14 G490E, G490A,
491 13 E491G,
492 13
493 12 R493K,
494 11
495 11
496 10 K496N, K496N, K496M,
497 9 S497C,
498 8
499 8
500 7 E500K,
501 5 D501G,
502 4
503 0 P503S,
504 4 R504T,
505 5 A505E,
506 7 M506K,
507 8 p.N507_L515dup,
508 8
509 9
510 10
511 11
512 11 T512I,
513 12 R513P, R513H, c.1537delC, R513C,
514 13 G514C,
515 13
516 14
517 14 R517S, R517S,
518 15