SCN5A Variant R526H
Summary of observed carriers, functional annotations, and structural context for SCN5A R526H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/30 effective observations
Estimated BrS1 penetrance
25%
7/30 effective observations
Total carriers
20
6 BrS1 · 0 LQT3 · 14 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
-0.94 | 0 | 2.91 | 0.476 | 14 | 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
Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
---|---|---|---|---|---|---|---|
24795344 | 2014 | 2 | 0 | 2 | 0 | ||
19412328 | 2008 | 1 | 0 | 0 | 1 | DCM | |
23321620 | 2013 | 1 | 0 | 1 | 0 | ||
27554632 | 2017 | 4 | 0 | 1 | 3 | CM | |
20129283 | 2010 | 1 | 0 | 1 | 0 | ||
20129283 | 2010 | 1 | 0 | 1 | 0 | ||
Literature, cohort, and gnomAD | – | 20 | 14 | 0 | 6 | – | |
Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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.
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
Neighbour residue | Distance (Å) | Observed variants |
---|---|---|
511 | 15 | |
512 | 14 | T512I, |
513 | 14 | R513H, R513C, R513P, c.1537delC, |
514 | 13 | G514C, |
515 | 13 | |
516 | 12 | |
517 | 11 | R517S, R517S, |
518 | 11 | |
519 | 10 | S519F, |
520 | 9 | M520V, M520R, |
521 | 8 | K521E, c.1562delA, |
522 | 8 | P522S, |
523 | 7 | R523S, R523C, R523H, |
524 | 5 | S524Y, c.1570_1571insG |
525 | 4 | S525G, |
526 | 0 | R526H, R526C, |
527 | 4 | G527R, G527R, |
528 | 5 | S528R, S528R, S528R, |
529 | 7 | |
530 | 8 | F530V, F530S, |
531 | 8 | T531I, T531A, |
532 | 9 | F532C, F532L, F532L, F532L, |
533 | 10 | R533H, R533S, R533C, |
534 | 11 | |
535 | 11 | R535X, R535Q, R535G, |
536 | 12 | D536H, |
537 | 13 | |
538 | 13 | G538D, |
539 | 14 | |
540 | 14 | |
541 | 15 |