SCN5A Variant C896S
Summary of observed carriers, functional annotations, and structural context for SCN5A C896S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
14%
0/11 effective observations
Estimated BrS1 penetrance
49%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -9.53 | 0.012 | -0.11 | 0.92 | 65 | 12 |
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 |
|---|---|---|---|---|---|---|---|
| 11901046 | 2002 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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) |
|---|---|---|---|---|---|---|
| 11901046 | 2002 |
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 | 9 | I891T, I891N, |
| 890 | 11 | I890T, |
| 901 | 13 | E901K, S901L, |
| 919 | 13 | |
| 896 | 0 | C896S, C896S, |
| 895 | 4 | L895F, |
| 1417 | 10 | |
| 894 | 7 | I894M, |
| 1457 | 11 | |
| 1453 | 12 | |
| 1455 | 10 | |
| 1447 | 14 | |
| 372 | 11 | |
| 1452 | 14 | |
| 1461 | 14 | T1461S, T1461S, |
| 926 | 9 | |
| 371 | 13 | Q371E, |
| 1711 | 14 | c.5131delG, |
| 928 | 11 | L928P, |
| 1450 | 12 | |
| 925 | 13 | I925F, |
| 887 | 14 | |
| 1451 | 10 | V1451D, V1451L, |
| 934 | 13 | |
| 1458 | 8 | S1458Y, |
| 933 | 15 | |
| 935 | 14 | L935P, |
| 897 | 5 | G897R, G897E, G897R, |
| 924 | 13 | V924I, |
| 927 | 7 | N927K, N927K, N927S, |
| 854 | 15 | c.2559delT, |
| 1422 | 10 | M1422R, |
| 1418 | 5 | |
| 902 | 12 | |
| 892 | 6 | F892I, |
| 373 | 12 | |
| 849 | 14 | |
| 888 | 11 | |
| 898 | 7 | |
| 893 | 7 | R893H, R893C, |
| 921 | 15 | |
| 922 | 10 | V922I, |
| 405 | 14 | |
| 1462 | 11 | |
| 1412 | 15 | L1412F, |
| 920 | 14 | |
| 889 | 10 | |
| 1709 | 15 | T1709M, T1709R, p.T1709del, |
| 1420 | 12 | G1420P, G1420D, G1420R, G1420V, |
| 843 | 14 | T843A, |
| 900 | 13 | |
| 1456 | 14 | |
| 930 | 11 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 7 | c.4376_4379delTCTT, |
| 1460 | 14 | F1460L, F1460L, F1460L, |
| 1425 | 12 | |
| 1454 | 8 | |
| 1424 | 15 | I1424V, |
| 929 | 13 | |
| 1448 | 15 | I1448T, I1448L, |
| 1421 | 8 | |
| 847 | 13 | |
| 846 | 11 | L846R, |
| 903 | 15 | p.M903CfsX29, |
| 367 | 15 | R367C, R367L, R367H, |
| 1416 | 9 | c.4245+1G>C, c.4245+1G>A, A1416E, A1416G, c.4245+2T>A, |
| 853 | 13 | |
| 1760 | 14 | |
| 370 | 12 | T370M, |
| 879 | 13 | W879R, W879R, |
| 923 | 9 | |
| 899 | 10 | |
| 1710 | 13 | S1710L, |
| 1415 | 10 | |
| 850 | 11 | c.2549_2550insTG, V850M, |
| 932 | 12 | |
| 1419 | 10 | K1419E, |
| 1414 | 13 | Q1414H, Q1414H, |
| 931 | 8 | |
| 1463 | 12 | N1463Y, |
| 1413 | 15 |