SCN5A Variant R893C
Summary of observed carriers, functional annotations, and structural context for SCN5A R893C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/16 effective observations
Estimated BrS1 penetrance
42%
6/16 effective observations
Total carriers
6
3 BrS1 · 0 LQT3 · 3 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.69 | 1 | -5.8 | 0.967 | 49 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 2 | 0 | 2 | 0 | ||
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| 30371189 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 6 | 3 | 0 | 3 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 |
|---|---|---|
| 891 | 8 | I891N, I891T, |
| 880 | 12 | |
| 888 | 10 | |
| 890 | 6 | I890T, |
| 901 | 7 | E901K, S901L, |
| 919 | 10 | |
| 896 | 7 | C896S, C896S, |
| 895 | 8 | L895F, |
| 1417 | 13 | |
| 1426 | 13 | |
| 894 | 5 | I894M, |
| 1447 | 13 | |
| 372 | 9 | |
| 926 | 13 | |
| 1429 | 15 | |
| 371 | 14 | Q371E, |
| 1711 | 15 | c.5131delG |
| 1450 | 13 | |
| 904 | 13 | W904X, |
| 887 | 11 | |
| 1451 | 13 | V1451L, V1451D, |
| 886 | 11 | H886P, H886Q, H886Q, |
| 1458 | 14 | S1458Y, |
| 376 | 15 | R376C, R376H, |
| 897 | 6 | G897R, G897R, G897E, |
| 1423 | 11 | D1423H, |
| 927 | 12 | N927S, N927K, N927K, |
| 854 | 13 | c.2559delT, |
| 1422 | 6 | M1422R, |
| 857 | 15 | G857D, |
| 1418 | 8 | |
| 902 | 7 | |
| 892 | 7 | F892I, |
| 373 | 10 | |
| 881 | 12 | |
| 898 | 4 | |
| 893 | 0 | R893C, R893H, |
| 922 | 11 | V922I, |
| 920 | 14 | |
| 889 | 7 | |
| 1420 | 10 | G1420R, G1420D, G1420V, G1420P, |
| 900 | 9 | |
| 1459 | 14 | c.4376_4379delTCTT, |
| 918 | 14 | |
| 1425 | 10 | |
| 1454 | 12 | |
| 1424 | 13 | I1424V, |
| 906 | 13 | |
| 878 | 10 | R878C, R878H, R878L, |
| 1421 | 7 | |
| 885 | 15 | |
| 903 | 11 | p.M903CfsX29, |
| 367 | 13 | R367C, R367H, R367L, |
| 1416 | 13 | c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G, |
| 853 | 13 | |
| 370 | 13 | T370M, |
| 877 | 12 | |
| 879 | 7 | W879R, W879R, |
| 923 | 10 | |
| 905 | 11 | |
| 375 | 15 | |
| 915 | 14 | C915R, |
| 899 | 8 | |
| 1710 | 15 | S1710L, |
| 1415 | 11 | |
| 850 | 13 | V850M, c.2549_2550insTG, |
| 1419 | 10 | K1419E, |
| 1414 | 14 | Q1414H, Q1414H, |
| 931 | 14 |