SCN5A Variant R475S
Summary of observed carriers, functional annotations, and structural context for SCN5A R475S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/20 effective observations
Estimated BrS1 penetrance
8%
1/20 effective observations
Total carriers
10
0 BrS1 · 0 LQT3 · 10 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 (%) |
|---|---|---|---|---|---|
| -4.73 | 0.972 | 0.98 | 0.474 | 22 | 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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 10 | 10 | 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) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 460 | 15 | |
| 461 | 14 | L461V, |
| 462 | 14 | E462A, E462K, |
| 463 | 13 | M463R, M463T, |
| 464 | 13 | |
| 465 | 12 | p.P465LfsX5, |
| 466 | 11 | L466F, L466F, |
| 467 | 11 | |
| 468 | 10 | P468L, |
| 469 | 9 | V469I, |
| 470 | 8 | N470K, N470K, |
| 471 | 8 | |
| 472 | 7 | |
| 473 | 5 | E473X, |
| 474 | 4 | R474G, R474K, |
| 475 | 0 | R475S, R475K, R475S, |
| 476 | 4 | |
| 477 | 5 | c.1428_1431delCAAG, |
| 478 | 7 | |
| 479 | 8 | |
| 480 | 8 | K480N, K480N, |
| 481 | 9 | R481Q, R481W, |
| 482 | 10 | M482I, M482I, M482I |
| 483 | 11 | |
| 484 | 11 | |
| 485 | 12 | |
| 486 | 13 | T486S, T486S, T486A, |
| 487 | 13 | |
| 488 | 14 | |
| 489 | 14 | |
| 490 | 15 | G490A, G490E, |