SCN5A Variant p.N1380del
Summary of observed carriers, functional annotations, and structural context for SCN5A p.N1380del. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/12 effective observations
Estimated BrS1 penetrance
65%
7/12 effective observations
Total carriers
2
2 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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 87 | 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 |
|---|---|---|---|---|---|---|---|
| 28159958 | 2017 | 5 | 0 | 0 | 5 | cardiac conduction | |
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 29759671 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 3 | 3 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 0 | 0 | 2 | – | |
| 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.
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 |
|---|---|---|
| 1386 | 7 | |
| 1394 | 11 | Y1394X, |
| 1430 | 10 | D1430N, |
| 1426 | 11 | |
| 1361 | 10 | |
| 1440 | 11 | W1440X, |
| 1382 | 6 | S1382I, |
| 1395 | 10 | |
| 1397 | 14 | c.4189delT, c.4190delA, |
| 1390 | 14 | |
| 1380 | 0 | N1380K, p.N1380del, |
| 1429 | 15 | |
| 1442 | 14 | Y1442C, Y1442N, |
| 1398 | 13 | V1398M, |
| 1396 | 10 | |
| 1362 | 6 | R1362S, c.4083delG, |
| 1433 | 15 | G1433W, G1433V, G1433R, |
| 1438 | 8 | P1438L |
| 1388 | 13 | |
| 1423 | 14 | D1423H, |
| 1387 | 11 | L1387F, |
| 1378 | 8 | V1378M, |
| 1437 | 7 | |
| 1384 | 12 | C1384Y, |
| 1431 | 13 | S1431C, |
| 1383 | 9 | Q1383X, |
| 1391 | 14 | G1391R, |
| 1366 | 12 | Q1366H, Q1366R, |
| 1381 | 5 | |
| 1360 | 13 | F1360C, |
| 1393 | 13 | L1393X, |
| 1427 | 12 | A1427E, A1427S, |
| 1385 | 11 | |
| 1365 | 7 | N1365S, |
| 1432 | 14 | R1432G, R1432S, |
| 1389 | 13 | |
| 1439 | 9 | Q1439H, Q1439R, |
| 1364 | 6 | I1364V, |
| 878 | 14 | R878L, R878H, R878C, |
| 1441 | 14 | E1441Q, |
| 1379 | 5 | |
| 1428 | 15 | A1428V, A1428S, |
| 1363 | 6 | C1363Y, |
| 1436 | 14 | |
| 1367 | 11 |