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 |