SCN5A Variant R523C
Summary of observed carriers, functional annotations, and structural context for SCN5A R523C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
18%
1/13 effective observations
Estimated BrS1 penetrance
11%
1/13 effective observations
Total carriers
3
0 BrS1 · 1 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -4.12 | 0.996 | -1.78 | 0.73 | 10 | 7 |
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 |
|---|---|---|---|---|---|---|---|
| 18752142 | 2008 | 1 | 1 | 0 | 0 | ||
| 18752973 | 2009 | 1 | 0 | 0 | 1 | SUDEP | |
| Literature, cohort, and gnomAD | – | 3 | 2 | 1 | 0 | – | |
| 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 |
|---|---|---|
| 508 | 15 | |
| 509 | 14 | |
| 510 | 14 | |
| 511 | 13 | |
| 512 | 13 | T512I, |
| 513 | 12 | R513H, R513C, c.1537delC, R513P, |
| 514 | 11 | G514C, |
| 515 | 11 | |
| 516 | 10 | |
| 517 | 9 | R517S, |
| 518 | 8 | |
| 519 | 8 | S519F, |
| 520 | 7 | M520R, M520V, |
| 521 | 5 | K521E, c.1562delA, |
| 522 | 4 | P522S, |
| 523 | 0 | R523S, R523H, R523C, |
| 524 | 4 | S524Y, c.1570_1571insG, |
| 525 | 5 | S525G, |
| 526 | 7 | R526H, R526C, |
| 527 | 8 | G527R, |
| 528 | 8 | S528R, |
| 529 | 9 | |
| 530 | 10 | F530V, F530S, |
| 531 | 11 | T531A, T531I, |
| 532 | 11 | F532C, F532L, |
| 533 | 12 | R533C, R533S, R533H |
| 534 | 13 | |
| 535 | 13 | R535X, R535Q, R535G, |
| 536 | 14 | D536H, |
| 537 | 14 | |
| 538 | 15 | G538D, |