SCN5A Variant R513H

Summary of observed carriers, functional annotations, and structural context for SCN5A R513H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

21%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

R513H is present in 1 alleles 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 (%)
0.64 0 2 0.453 29 0

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
24529773 2014 1 0 0 1 SUNDS
27554632 2017 1 0 0 1 CM
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 13 0 2 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
24529773 2014
27554632 2017

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 R513H.
Neighbour residue Distance (Å) Observed variants
498 15
499 14
500 14 E500K,
501 13 D501G,
502 13
503 12 P503S,
504 11 R504T,
505 11 A505E,
506 10 M506K,
507 9 p.N507_L515dup,
508 8
509 8
510 7
511 5
512 4 T512I,
513 0 R513C, c.1537delC, R513H, R513P,
514 4 G514C,
515 5
516 7
517 8 R517S, R517S,
518 8
519 9 S519F,
520 10 M520V, M520R,
521 11 K521E, c.1562delA,
522 11 P522S,
523 12 R523S, R523C, R523H,
524 13 c.1570_1571insG, S524Y,
525 13 S525G,
526 14 R526C, R526H,
527 14 G527R, G527R,
528 15 S528R, S528R, S528R