SCN5A Variant S519P

Summary of observed carriers, functional annotations, and structural context for SCN5A S519P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

35%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

S519P 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 3 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 0.502 51 1

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 12 0 3

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 S519P.
Neighbour residue Distance (Å) Observed variants
504 15 R504T,
505 14 A505E,
506 14 M506K,
507 13 p.N507_L515dup,
508 13
509 12
510 11
511 11
512 10 T512I,
513 9 R513P, c.1537delC, R513C, R513H,
514 8 G514C,
515 8
516 7
517 5 R517S, R517S,
518 4
519 0 S519F,
520 4 M520V, M520R,
521 5 K521E, c.1562delA,
522 7 P522S,
523 8 R523S, R523H, R523C,
524 8 c.1570_1571insG, S524Y,
525 9 S525G,
526 10 R526C, R526H,
527 11 G527R, G527R,
528 11 S528R, S528R, S528R,
529 12
530 13 F530S, F530V,
531 13 T531A, T531I,
532 14 F532C, F532L, F532L, F532L,
533 14 R533H, R533C, R533S,
534 15