SCN5A Variant R367C
Summary of observed carriers, functional annotations, and structural context for SCN5A R367C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
21%
2/18 effective observations
Estimated BrS1 penetrance
45%
8/18 effective observations
Total carriers
8
3 BrS1 · 2 LQT3 · 3 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.85 | 1 | -4.45 | 0.956 | 71 | 15 |
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 |
|---|---|---|---|---|---|---|---|
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 21273195 | 2011 | 3 | 0 | 3 | 0 | ||
| 22885917 | 2012 | 1 | 0 | 1 | 0 | ||
| 26921764 | 2016 | 1 | 0 | 1 | 0 | ||
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 19716085 | 2009 | 2 | 2 | 0 | 0 | ||
| 20129283 | 2010 | 2 | 0 | 2 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 8 | 3 | 2 | 3 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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 | 5 | |
| 919 | 13 | |
| 901 | 11 | E901K, S901L, |
| 276 | 13 | L276P, L276Q, |
| 363 | 6 | |
| 896 | 15 | C896S, |
| 404 | 15 | L404Q, L404V, |
| 348 | 13 | P348A, |
| 360 | 11 | |
| 396 | 11 | V396A, V396L, |
| 894 | 12 | I894M, |
| 355 | 11 | F355I, F355C, |
| 372 | 4 | |
| 401 | 12 | S401P, |
| 371 | 8 | Q371E, |
| 1711 | 12 | c.5131delG, |
| 928 | 15 | L928P, |
| 361 | 10 | |
| 904 | 9 | W904X, |
| 366 | 7 | |
| 365 | 7 | |
| 1706 | 13 | Q1706H, |
| 376 | 9 | R376H, R376C, |
| 354 | 11 | |
| 897 | 10 | G897E, G897R, |
| 927 | 15 | N927K, N927S, |
| 369 | 9 | M369K, |
| 378 | 12 | |
| 902 | 12 | |
| 402 | 15 | F402L, |
| 349 | 11 | D349N, |
| 373 | 6 | |
| 1712 | 14 | G1712S, G1712C, |
| 379 | 13 | |
| 898 | 10 | |
| 893 | 13 | R893H, R893C, |
| 922 | 15 | V922I, |
| 272 | 14 | |
| 397 | 11 | I397F, I397T, I397V, |
| 405 | 14 | |
| 362 | 10 | |
| 261 | 12 | |
| 920 | 11 | |
| 1709 | 13 | T1709R, T1709M, p.T1709del, |
| 900 | 6 | |
| 392 | 13 | |
| 393 | 11 | |
| 916 | 12 | |
| 264 | 13 | |
| 347 | 14 | |
| 351 | 13 | G351D, G351V, G351S, G351C |
| 265 | 12 | A265V, |
| 374 | 8 | W374G, |
| 350 | 12 | H350Q, |
| 358 | 15 | |
| 903 | 9 | p.M903CfsX29, |
| 367 | 0 | R367L, R367C, R367H, |
| 359 | 13 | p.A359PfsX12, A359T, |
| 370 | 7 | T370M, |
| 381 | 12 | c.1140+1G>A, c.1141-3C>A, |
| 923 | 11 | |
| 905 | 14 | |
| 375 | 10 | |
| 352 | 12 | Y352C, |
| 368 | 5 | |
| 899 | 6 | |
| 1710 | 14 | S1710L, |
| 380 | 12 | |
| 915 | 15 | C915R, |
| 268 | 13 | G268S, |
| 377 | 6 | |
| 400 | 13 | G400A, G400R, G400E, |
| 1419 | 14 | K1419E, |
| 353 | 9 | T353I, |
| 907 | 13 |