SCN5A Variant R433C
Summary of observed carriers, functional annotations, and structural context for SCN5A R433C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/13 effective observations
Estimated BrS1 penetrance
10%
1/13 effective observations
Total carriers
3
0 BrS1 · 0 LQT3 · 3 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 (%) |
|---|---|---|---|---|---|
| -4.63 | 0.978 | -4.43 | 0.589 | 4 | 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 |
|---|---|---|---|---|---|---|---|
| 29167113 | 2018 | 1 | 0 | 0 | 1 | IBS | |
| Literature, cohort, and gnomAD | – | 3 | 3 | 0 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 29167113 | 2018 | HEK | 43 | -2.2 | -16.5 |
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 |
|---|---|---|
| 418 | 15 | E418K, |
| 419 | 14 | Q419X, |
| 420 | 14 | |
| 421 | 13 | |
| 422 | 13 | |
| 423 | 12 | |
| 424 | 11 | I424M, |
| 425 | 11 | A425P, A425T, |
| 426 | 10 | |
| 427 | 9 | |
| 428 | 8 | E428K, |
| 429 | 8 | E429K, p.E429del, |
| 430 | 7 | K430E, |
| 431 | 5 | |
| 432 | 4 | |
| 433 | 0 | R433H, R433S, R433C, |
| 434 | 4 | |
| 435 | 5 | |
| 436 | 7 | |
| 437 | 8 | A437V, |
| 438 | 8 | M438T, M438L, M438L, |
| 439 | 9 | E439V, E439K, |
| 440 | 10 | |
| 441 | 11 | L441F, |
| 442 | 11 | |
| 443 | 12 | |
| 444 | 13 | E444fsX14, |
| 445 | 13 | H445Q, H445Y, H445D, H445Q, |
| 446 | 14 | E446K, |
| 447 | 14 | c.1339-24G>A, A447G, A447S, c.1338+2T>A, |
| 448 | 15 |