SCN5A Variant S499L

Summary of observed carriers, functional annotations, and structural context for SCN5A S499L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

15%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

S499L 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 1 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 0.537 16 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 14 0 1 – –

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 S499L.
Neighbour residue Distance (Å) Observed variants
484 15
485 14
486 14 T486S, T486S, T486A
487 13
488 13
489 12
490 11 G490A, G490E,
491 11 E491G,
492 10
493 9 R493K,
494 8
495 8
496 7 K496N, K496M, K496N,
497 5 S497C,
498 4
499 0
500 4 E500K,
501 5 D501G,
502 7
503 8 P503S,
504 8 R504T,
505 9 A505E,
506 10 M506K,
507 11 p.N507_L515dup,
508 11
509 12
510 13
511 13
512 14 T512I,
513 14 R513P, c.1537delC, R513H, R513C,
514 15 G514C,