SCN5A Variant R376C
Summary of observed carriers, functional annotations, and structural context for SCN5A R376C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/11 effective observations
Estimated BrS1 penetrance
24%
2/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5 | 1 | -3.78 | 0.941 | 29 | 2 |
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 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 3 | 3 | 0 | 0 | ||
| 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.
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 |
|---|---|---|
| 364 | 12 | |
| 1702 | 14 | |
| 901 | 10 | E901K, S901L, |
| 276 | 11 | L276Q, L276P, |
| 363 | 14 | |
| 348 | 8 | P348A, |
| 279 | 15 | |
| 355 | 14 | F355I, F355C, |
| 1715 | 12 | |
| 1687 | 10 | |
| 372 | 10 | |
| 371 | 13 | Q371E, |
| 1711 | 11 | c.5131delG, |
| 904 | 11 | W904X, |
| 1706 | 11 | Q1706H, Q1706H, |
| 1716 | 13 | p.L1716SfsX71 |
| 376 | 0 | R376C, R376H, |
| 1714 | 14 | D1714G, |
| 384 | 13 | S384T, |
| 1688 | 14 | |
| 354 | 12 | |
| 897 | 15 | G897R, G897R, G897E, |
| 1423 | 15 | D1423H, |
| 1692 | 12 | |
| 1422 | 15 | M1422R, |
| 378 | 9 | |
| 902 | 14 | |
| 349 | 7 | D349N, |
| 373 | 7 | |
| 1712 | 10 | G1712S, G1712C, |
| 379 | 6 | |
| 1703 | 14 | |
| 898 | 12 | |
| 893 | 15 | R893C, R893H, |
| 1709 | 14 | p.T1709del, T1709R, T1709M, |
| 325 | 11 | L325R, |
| 1420 | 13 | G1420R, G1420D, G1420V, G1420P, |
| 900 | 10 | |
| 324 | 10 | |
| 393 | 13 | |
| 1713 | 15 | |
| 383 | 11 | |
| 323 | 13 | |
| 347 | 12 | |
| 382 | 12 | |
| 351 | 12 | G351S, G351C, G351D, G351V, |
| 374 | 9 | W374G, |
| 1689 | 12 | D1689N, |
| 350 | 11 | H350Q, H350Q, |
| 903 | 14 | p.M903CfsX29, |
| 367 | 9 | R367C, R367H, R367L, |
| 370 | 15 | T370M, |
| 381 | 10 | c.1140+1G>A, c.1141-3C>A, |
| 1686 | 12 | |
| 322 | 13 | |
| 905 | 14 | |
| 375 | 5 | |
| 1691 | 14 | |
| 352 | 14 | Y352C, |
| 368 | 12 | |
| 899 | 13 | |
| 1710 | 14 | S1710L, |
| 380 | 6 | |
| 377 | 6 | |
| 1419 | 12 | K1419E, |
| 353 | 9 | T353I, |