SCN5A Variant D1430N
Summary of observed carriers, functional annotations, and structural context for SCN5A D1430N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/12 effective observations
Estimated BrS1 penetrance
59%
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 (%) |
|---|---|---|---|---|---|
| -4.74 | 1 | -1.04 | 0.941 | 73 | 4 |
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 |
|---|---|---|---|---|---|---|---|
| 23612926 | 2013 | 2 | 0 | 2 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 23612926 | 2013 | tsA201 | 0 |
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 |
|---|---|---|
| 880 | 15 | |
| 1355 | 12 | |
| 1357 | 13 | A1357V, |
| 1386 | 12 | |
| 1430 | 0 | D1430N, |
| 1352 | 15 | |
| 1426 | 5 | |
| 1445 | 12 | Y1445H, |
| 1361 | 9 | |
| 1447 | 13 | |
| 1444 | 9 | L1444I, |
| 1440 | 7 | W1440X, |
| 1382 | 11 | S1382I, |
| 1395 | 13 | |
| 1397 | 13 | c.4189delT, c.4190delA, |
| 1449 | 14 | Y1449S, Y1449C |
| 1380 | 10 | p.N1380del, N1380K, N1380K, |
| 1429 | 5 | |
| 1442 | 8 | Y1442N, Y1442C, |
| 1450 | 13 | |
| 1398 | 11 | V1398M, |
| 886 | 13 | H886P, H886Q, H886Q, |
| 1358 | 12 | G1358R, G1358R, G1358W, |
| 1396 | 13 | |
| 1362 | 7 | c.4083delG, R1362S, R1362S, |
| 1433 | 9 | G1433R, G1433R, G1433W, G1433V, |
| 1438 | 5 | P1438L, |
| 1388 | 14 | |
| 1423 | 11 | D1423H, |
| 1387 | 12 | L1387F, L1387F, |
| 1437 | 8 | |
| 1431 | 4 | S1431C, |
| 1422 | 13 | M1422R, |
| 1383 | 12 | Q1383X, |
| 1359 | 8 | K1359M, K1359N, K1359N, |
| 1434 | 12 | c.4299_4300insG, c.4299+1delG, c.4299+1G>T, c.4299+28C>T, c.4299+2T>A, c.4299delG, c.4299G>A, Y1434X, c.4300-1G>A, c.4300-2A>T, |
| 1356 | 10 | c.4066_4068delTT, |
| 1381 | 14 | |
| 889 | 15 | |
| 1420 | 15 | G1420R, G1420D, G1420V, G1420P, |
| 1435 | 14 | |
| 1360 | 8 | F1360C, |
| 1401 | 14 | |
| 1425 | 9 | |
| 1427 | 5 | A1427S, A1427E, |
| 1446 | 11 | |
| 1424 | 10 | I1424V, |
| 1432 | 8 | R1432G, R1432S, R1432S, |
| 1439 | 6 | Q1439R, Q1439H, Q1439H, |
| 1364 | 13 | I1364V, |
| 878 | 10 | R878C, R878H, R878L, |
| 1400 | 14 | V1400I, |
| 1421 | 15 | |
| 1443 | 8 | N1443S, |
| 1441 | 9 | E1441Q, |
| 1379 | 15 | |
| 877 | 14 | |
| 879 | 12 | W879R, W879R, |
| 1428 | 5 | A1428S, A1428V, |
| 1363 | 12 | C1363Y, |
| 1436 | 11 | |
| 1402 | 13 |