SCN5A Variant p.Q1475NfsX6
Summary of observed carriers, functional annotations, and structural context for SCN5A p.Q1475NfsX6. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
74%
4/11 effective observations
Estimated BrS1 penetrance
8%
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 3 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 2 | 93 |
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 |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 12 | 3 | 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) |
|---|---|---|---|---|---|---|
| 30059973 | 2018 |
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 |
|---|---|---|
| 1328 | 13 | V1328M, |
| 939 | 14 | L939F, |
| 1480 | 9 | c.4437+5G>A, c.4438-1C>T, |
| 1773 | 11 | |
| 943 | 12 | S943N, |
| 1486 | 14 | F1486L, p.F1486del, F1486L, F1486L, |
| 1472 | 7 | p.N1472del, N1472S, |
| 1777 | 14 | V1777M, V1777L, V1777L |
| 1485 | 12 | |
| 1487 | 10 | M1487L, M1487L, M1487K, |
| 1333 | 13 | |
| 1492 | 13 | |
| 1477 | 7 | K1477N, K1477N, |
| 1471 | 8 | |
| 1470 | 11 | |
| 1478 | 5 | K1478E, |
| 1776 | 15 | |
| 944 | 12 | |
| 1329 | 11 | G1329S, |
| 1769 | 13 | |
| 1766 | 14 | M1766L, M1766V, M1766L, M1766T, |
| 1774 | 14 | N1774D, c.5321_5324dupACTT, |
| 1479 | 5 | |
| 1473 | 8 | F1473S, F1473C, |
| 1468 | 12 | V1468F, V1468A, |
| 1474 | 5 | |
| 1324 | 14 | |
| 1481 | 10 | G1481R, G1481R, G1481E, G1481V, |
| 1327 | 14 | |
| 1330 | 12 | A1330T, A1330P, A1330D, |
| 1772 | 15 | L1772V, |
| 1488 | 14 | T1488R, |
| 1323 | 13 | V1323G, |
| 1770 | 14 | I1770V, |
| 1482 | 9 | |
| 1322 | 11 | c.3963+2T>C, c.3963+4A>G, |
| 1326 | 10 | A1326S, |
| 1332 | 14 | P1332Q, P1332L, |
| 1467 | 13 | |
| 1476 | 6 | Q1476X, Q1476R, |
| 1484 | 7 | |
| 1475 | 0 | p.Q1475NfsX6, Q1475L, |
| 1469 | 12 | I1469V, |
| 1483 | 11 | Q1483H, Q1483H, |
| 1325 | 11 | N1325S, |
| 1489 | 12 | E1489D, E1489D, |