SCN5A Variant c.4066_4068delTT
Summary of observed carriers, functional annotations, and structural context for SCN5A c.4066_4068delTT. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/13 effective observations
Estimated BrS1 penetrance
59%
7/13 effective observations
Total carriers
3
3 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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 68 | 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 |
|---|---|---|---|---|---|---|---|
| 21397042 | 2011 | 3 | 0 | 3 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 0 | 0 | 3 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 21397042 | 2011 |
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 | 4 | |
| 1403 | 9 | |
| 1357 | 6 | A1357V, |
| 1430 | 10 | D1430N, |
| 808 | 13 | R808P, R808H, R808C, |
| 1352 | 5 | |
| 1426 | 13 | |
| 1406 | 13 | G1406E, G1406R, G1406R, |
| 1445 | 12 | Y1445H, |
| 1453 | 12 | |
| 1361 | 11 | |
| 1447 | 13 | |
| 1444 | 13 | L1444I, |
| 1351 | 9 | M1351V, M1351R, |
| 739 | 11 | |
| 1397 | 13 | c.4189delT, c.4190delA, |
| 1449 | 8 | Y1449C, Y1449S, |
| 1452 | 14 | |
| 812 | 15 | L812Q, |
| 1350 | 11 | I1350L, I1350T, |
| 1429 | 9 | |
| 1442 | 15 | Y1442N, Y1442C, |
| 806 | 14 | V806M, |
| 1450 | 9 | |
| 1398 | 11 | V1398M, |
| 1411 | 10 | |
| 1451 | 14 | V1451L, V1451D, |
| 1353 | 7 | V1353M, |
| 1407 | 11 | |
| 737 | 12 | |
| 1410 | 14 | |
| 1358 | 8 | G1358R, G1358R, G1358W, |
| 1362 | 13 | c.4083delG, R1362S, R1362S, |
| 1433 | 9 | G1433V, G1433W, G1433R, G1433R, |
| 1438 | 12 | P1438L, |
| 1348 | 11 | F1348L, F1348L, F1348L, |
| 1404 | 11 | |
| 1423 | 14 | D1423H, |
| 1437 | 15 | |
| 1349 | 10 | |
| 1431 | 7 | S1431C, |
| 1422 | 15 | M1422R, |
| 1346 | 15 | L1346I, L1346P, |
| 805 | 13 | S805L, |
| 1359 | 5 | K1359M, K1359N, K1359N, |
| 1356 | 0 | c.4066_4068delTT, |
| 1434 | 8 | c.4299+28C>T, c.4300-2A>T, c.4299+1G>T, c.4299delG, c.4299G>A, c.4299_4300insG, c.4300-1G>A, c.4299+1delG, Y1434X, c.4299+2T>A, |
| 1412 | 10 | L1412F, |
| 1408 | 9 | G1408R, G1408R, |
| 1435 | 14 | |
| 1360 | 7 | F1360C, |
| 1401 | 9 | |
| 1425 | 10 | |
| 1354 | 8 | |
| 1427 | 8 | A1427S, A1427E, |
| 1446 | 8 | |
| 1424 | 9 | I1424V, |
| 738 | 13 | |
| 1432 | 12 | R1432S, R1432G, R1432S, |
| 1448 | 13 | I1448L, I1448T, |
| 1439 | 15 | Q1439H, Q1439R, Q1439H, |
| 1405 | 12 | V1405L, V1405L, V1405M, |
| 809 | 13 | |
| 1409 | 14 | Y1409X, Y1409C, |
| 1400 | 11 | V1400I, |
| 1421 | 15 | |
| 1443 | 11 | N1443S, |
| 1347 | 14 | |
| 1415 | 13 | |
| 1428 | 6 | A1428S, A1428V, |
| 1436 | 14 | |
| 1414 | 15 | Q1414H, Q1414H, |
| 1402 | 5 |