SCN5A Variant K1477N
Summary of observed carriers, functional annotations, and structural context for SCN5A K1477N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
59%
3/11 effective observations
Estimated BrS1 penetrance
7%
0/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.67 | 0.951 | 0.69 | 0.806 | 4 | 64 |
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 |
|---|---|---|---|---|---|---|---|
| 23558814 | 2013 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 13 | 2 | 0 | – | – |
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) |
|---|---|---|---|---|---|---|
| 23558814 | 2013 |
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 |
|---|---|---|
| 1659 | 14 | |
| 1778 | 13 | |
| 1480 | 6 | c.4437+5G>A, c.4438-1C>T, |
| 1773 | 7 | |
| 1653 | 11 | |
| 1472 | 10 | p.N1472del, N1472S, |
| 1771 | 12 | I1771T, |
| 1652 | 11 | M1652T, M1652R, |
| 1777 | 9 | V1777M, V1777L, V1777L |
| 1487 | 13 | M1487K, M1487L, M1487L, |
| 1320 | 13 | M1320I, M1320I, M1320I, |
| 1492 | 11 | |
| 1656 | 11 | |
| 1477 | 0 | K1477N, K1477N, |
| 1471 | 11 | |
| 1779 | 15 | T1779M, |
| 1493 | 14 | K1493X, K1493R, p.K1493del, |
| 1470 | 10 | |
| 1478 | 6 | K1478E, |
| 1776 | 11 | |
| 1767 | 14 | Y1767C, |
| 1660 | 14 | I1660S, I1660V, |
| 1654 | 15 | |
| 1329 | 14 | G1329S, |
| 1769 | 10 | |
| 1766 | 12 | M1766V, M1766L, M1766T, M1766L, |
| 1319 | 11 | G1319V, |
| 1495 | 13 | Y1495S, |
| 1649 | 13 | A1649V, |
| 1768 | 14 | I1768V, |
| 1774 | 8 | N1774D, c.5321_5324dupACTT, |
| 1479 | 8 | |
| 1473 | 6 | F1473C, F1473S, |
| 1468 | 15 | V1468F, V1468A, |
| 1657 | 13 | |
| 1496 | 12 | |
| 1474 | 6 | |
| 1324 | 13 | |
| 1481 | 7 | G1481R, G1481V, G1481E, G1481R, |
| 1327 | 14 | |
| 1781 | 14 | E1781D, E1781G, E1781D, |
| 1318 | 13 | |
| 1330 | 15 | A1330P, A1330D, A1330T, |
| 1772 | 11 | L1772V, |
| 1321 | 13 | R1321K, |
| 1323 | 10 | V1323G, |
| 1780 | 14 | E1780G, |
| 1770 | 8 | I1770V, |
| 1482 | 8 | |
| 1322 | 7 | c.3963+2T>C, c.3963+4A>G, |
| 1326 | 10 | A1326S, |
| 1467 | 15 | |
| 1476 | 6 | Q1476R, Q1476X, |
| 1775 | 14 | F1775V, p.F1775LfsX15, |
| 1484 | 12 | |
| 1655 | 13 | |
| 1475 | 7 | Q1475L, p.Q1475NfsX6, |
| 1469 | 12 | I1469V, |
| 1483 | 12 | Q1483H, Q1483H, |
| 1325 | 11 | N1325S, |
| 1489 | 12 | E1489D, E1489D, |