SCN5A Variant K1359N
Summary of observed carriers, functional annotations, and structural context for SCN5A K1359N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/11 effective observations
Estimated BrS1 penetrance
42%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.66 | 1 | -0.26 | 0.904 | 52 | 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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 | 7 | |
| 1403 | 8 | |
| 1357 | 5 | A1357V, |
| 741 | 14 | p.M741_T742delinsI , |
| 1430 | 8 | D1430N, |
| 1352 | 9 | |
| 1426 | 12 | |
| 1445 | 14 | Y1445H, |
| 1361 | 7 | |
| 1351 | 13 | M1351R, M1351V, |
| 1444 | 14 | L1444I, |
| 739 | 9 | |
| 1395 | 11 | |
| 1397 | 10 | c.4190delA, c.4189delT, |
| 1449 | 12 | Y1449S, Y1449C, |
| 1350 | 14 | I1350L, I1350T, |
| 1429 | 10 | |
| 1442 | 13 | Y1442C, Y1442N, |
| 1450 | 13 | |
| 1398 | 10 | V1398M, |
| 1411 | 14 | |
| 1353 | 10 | V1353M, |
| 1407 | 13 | |
| 737 | 13 | |
| 1358 | 4 | G1358W, G1358R, G1358R, |
| 1396 | 13 | |
| 1362 | 10 | R1362S, R1362S, c.4083delG, |
| 1433 | 5 | G1433R, G1433W, G1433V, G1433R, |
| 1438 | 8 | P1438L, |
| 1388 | 13 | |
| 1404 | 13 | |
| 1423 | 15 | D1423H, |
| 1387 | 14 | L1387F, L1387F, |
| 1437 | 10 | |
| 1349 | 14 | |
| 1431 | 5 | S1431C, |
| 805 | 14 | S805L, |
| 1359 | 0 | K1359N, K1359M, K1359N, |
| 1356 | 5 | c.4066_4068delTT, |
| 1434 | 5 | c.4299G>A, c.4299_4300insG, c.4299delG, c.4299+28C>T, c.4299+1G>T, c.4299+1delG, c.4300-2A>T, c.4299+2T>A, c.4300-1G>A, Y1434X, |
| 1412 | 15 | L1412F, |
| 1408 | 13 | G1408R, G1408R, |
| 1435 | 9 | |
| 1360 | 5 | F1360C, |
| 1401 | 9 | |
| 1425 | 13 | |
| 1354 | 11 | |
| 1427 | 8 | A1427S, A1427E, |
| 1446 | 11 | |
| 1424 | 12 | I1424V, |
| 738 | 13 | |
| 1432 | 9 | R1432S, R1432G, R1432S, |
| 1439 | 12 | Q1439H, Q1439H, Q1439R, |
| 1405 | 15 | V1405M, V1405L, V1405L, |
| 740 | 13 | p.N740del, |
| 1400 | 12 | V1400I, |
| 1443 | 10 | N1443S, |
| 1428 | 7 | A1428V, A1428S, |
| 1363 | 14 | C1363Y, |
| 1436 | 9 | |
| 1402 | 8 |