SCN5A Variant R878C
Summary of observed carriers, functional annotations, and structural context for SCN5A R878C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
0/46 effective observations
Estimated BrS1 penetrance
83%
38/46 effective observations
Total carriers
36
32 BrS1 · 0 LQT3 · 4 unaffected
Variant features alone are equivalent to phenotyping 6 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.6 | 1 | -5.06 | 0.961 | 93 | 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 |
|---|---|---|---|---|---|---|---|
| 18616619 | 2008 | 4 | 0 | 3 | 0 | ||
| 22840528 | 2012 | 1 | 0 | 1 | 0 | ||
| 24721456 | 2014 | 2 | 0 | 2 | 0 | ||
| 26036855 | 2016 | 11 | 0 | 11 | 0 | ||
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 28781330 | 2017 | 30 | 0 | 27 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 36 | 4 | 0 | 32 | – | |
| Variant features alone | – | 15 | 9 | 0 | 6 | – | – |
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) |
|---|---|---|---|---|---|---|
| 20384651 | 2010 | 0 | ||||
| 22739120 | 2012 | HEK | 0 | |||
| 18616619 | 2008 | HEK | 0 | |||
| 22840528 | 2012 | |||||
| 24721456 | 2014 | |||||
| 26036855 | 2016 | |||||
| 28341781 | 2017 | |||||
| 28781330 | 2017 | |||||
| 20539757 | 2010 | |||||
| 20129283 | 2010 | |||||
| 29325976 | 2018 | |||||
| 30059973 | 2018 |
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 |
|---|---|---|
| 880 | 9 | |
| 888 | 15 | |
| 890 | 11 | I890T, |
| 901 | 9 | E901K, S901L, |
| 1430 | 10 | D1430N, |
| 1426 | 5 | |
| 894 | 15 | I894M, |
| 1447 | 14 | |
| 1444 | 12 | L1444I |
| 1440 | 7 | W1440X, |
| 1380 | 14 | p.N1380del, N1380K, N1380K, |
| 1429 | 10 | |
| 1442 | 15 | Y1442N, Y1442C, |
| 1450 | 15 | |
| 887 | 13 | |
| 886 | 9 | H886P, H886Q, H886Q, |
| 1362 | 13 | c.4083delG, R1362S, R1362S, |
| 1438 | 14 | P1438L, |
| 871 | 13 | |
| 1423 | 7 | D1423H, |
| 876 | 9 | |
| 1431 | 14 | S1431C, |
| 1422 | 7 | M1422R, |
| 902 | 11 | |
| 882 | 14 | |
| 892 | 15 | F892I, |
| 881 | 13 | |
| 898 | 12 | |
| 893 | 10 | R893C, R893H, |
| 889 | 10 | |
| 1420 | 11 | G1420R, G1420D, G1420V, G1420P, |
| 900 | 14 | |
| 1360 | 15 | F1360C, |
| 872 | 13 | D872N, |
| 1425 | 9 | |
| 865 | 13 | |
| 1427 | 10 | A1427S, A1427E, |
| 1424 | 11 | I1424V, |
| 1439 | 13 | Q1439R, Q1439H, Q1439H, |
| 906 | 14 | |
| 874 | 12 | G874D, |
| 878 | 0 | R878C, R878H, R878L, |
| 1421 | 11 | |
| 885 | 14 | |
| 350 | 15 | H350Q, H350Q, |
| 1441 | 11 | E1441Q, |
| 877 | 6 | |
| 879 | 4 | W879R, W879R, |
| 883 | 14 | |
| 905 | 11 | |
| 875 | 12 | |
| 1428 | 12 | A1428S, A1428V, |
| 908 | 15 | |
| 873 | 14 | S873A, |
| 1419 | 15 | K1419E, |