SCN5A Variant L1412F
Summary of observed carriers, functional annotations, and structural context for SCN5A L1412F. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/11 effective observations
Estimated BrS1 penetrance
57%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 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 (%) |
|---|---|---|---|---|---|
| -3.9 | 1 | -1.86 | 0.899 | 83 | 6 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 1355 | 13 | |
| 1403 | 13 | |
| 1357 | 13 | A1357V, |
| 896 | 15 | C896S, C896S, |
| 1417 | 9 | |
| 1352 | 9 | |
| 1406 | 9 | G1406R, G1406R, G1406E, |
| 1340 | 15 | V1340I, |
| 1457 | 9 | |
| 1453 | 6 | |
| 1455 | 13 | |
| 1351 | 10 | M1351V, M1351R, |
| 1449 | 9 | Y1449S, Y1449C, |
| 1756 | 14 | I1756V |
| 1452 | 12 | |
| 1461 | 12 | T1461S, T1461S, |
| 1350 | 11 | I1350L, I1350T, |
| 1344 | 12 | F1344L, F1344S, F1344L, F1344L, |
| 1450 | 8 | |
| 1398 | 14 | V1398M, |
| 1411 | 4 | |
| 1451 | 12 | V1451L, V1451D, |
| 1353 | 11 | V1353M, |
| 1407 | 8 | |
| 1458 | 10 | S1458Y, |
| 1410 | 7 | |
| 1714 | 13 | D1714G, |
| 1348 | 8 | F1348L, F1348L, F1348L, |
| 1404 | 11 | |
| 1423 | 14 | D1423H, |
| 1349 | 7 | |
| 1753 | 13 | T1753A, |
| 1422 | 13 | M1422R, |
| 1346 | 10 | L1346I, L1346P, |
| 1418 | 11 | |
| 1359 | 15 | K1359M, K1359N, K1359N, |
| 1341 | 11 | |
| 1356 | 10 | c.4066_4068delTT, |
| 1462 | 12 | |
| 1412 | 0 | L1412F, |
| 1408 | 5 | G1408R, G1408R, |
| 735 | 15 | A735T, A735E, A735V, |
| 1420 | 11 | G1420R, G1420D, G1420V, G1420P, |
| 1456 | 12 | |
| 1360 | 13 | F1360C, |
| 1459 | 14 | c.4376_4379delTCTT, |
| 1401 | 10 | |
| 1425 | 11 | |
| 1713 | 13 | |
| 1454 | 9 | |
| 1338 | 15 | L1338V, |
| 1354 | 14 | |
| 1427 | 14 | A1427S, A1427E, |
| 1446 | 15 | |
| 1424 | 9 | I1424V, |
| 1448 | 14 | I1448L, I1448T, |
| 1405 | 10 | V1405M, V1405L, V1405L, |
| 1409 | 6 | Y1409C, Y1409X, |
| 1400 | 10 | V1400I, |
| 1421 | 10 | |
| 1343 | 13 | |
| 1345 | 7 | W1345C, W1345C, |
| 1717 | 14 | L1717P, |
| 1342 | 11 | |
| 1416 | 7 | c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G, |
| 1749 | 14 | I1749N, |
| 1347 | 11 | |
| 1415 | 5 | |
| 1428 | 12 | A1428S, A1428V, |
| 1419 | 12 | K1419E, |
| 1414 | 7 | Q1414H, Q1414H, |
| 1402 | 7 | |
| 1413 | 5 |