SCN5A Variant S516R

Summary of observed carriers, functional annotations, and structural context for SCN5A S516R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

23%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

S516R 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 0.559 30 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 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 S516R.
Neighbour residue Distance (Å) Observed variants
501 15 D501G,
502 14
503 14 P503S,
504 13 R504T,
505 13 A505E,
506 12 M506K,
507 11 p.N507_L515dup,
508 11
509 10
510 9
511 8
512 8 T512I,
513 7 c.1537delC, R513H, R513C, R513P,
514 5 G514C,
515 4
516 0
517 4 R517S, R517S,
518 5
519 7 S519F,
520 8 M520V, M520R,
521 8 c.1562delA, K521E,
522 9 P522S,
523 10 R523H, R523S, R523C,
524 11 c.1570_1571insG, S524Y,
525 11 S525G,
526 12 R526H, R526C,
527 13 G527R, G527R,
528 13 S528R, S528R, S528R,
529 14
530 14 F530V, F530S,
531 15 T531I, T531A,