SCN5A Variant P1332L
Summary of observed carriers, functional annotations, and structural context for SCN5A P1332L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
74%
8/17 effective observations
Estimated BrS1 penetrance
13%
2/17 effective observations
Total carriers
7
1 BrS1 · 6 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -9.74 | 1 | -3.1 | 0.922 | 9 | 72 |
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 |
|---|---|---|---|---|---|---|---|
| 17698727 | 2007 | 2 | 2 | 0 | 0 | ||
| 15136511 | 2004 | 1 | 1 | 0 | 0 | AV block | |
| 16244680 | 2005 | 1 | 1 | 0 | 0 | ||
| 18752142 | 2008 | 1 | 1 | 0 | 0 | ||
| 23631430 | 2013 | 1 | 1 | 0 | 0 | ||
| 24667783 | 2015 | 1 | 1 | 0 | 0 | ||
| 26940925 | 2016 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 7 | 0 | 6 | 1 | – | |
| Variant features alone | – | 15 | 12 | 2 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 17698727 | 2007 | HEK | 100 | -5 | -6.4 | 140 |
| 29791480 | 2018 | CHO | 104 | -8.35 | -9.84 | 267 |
| 15136511 | 2004 | |||||
| 16244680 | 2005 | |||||
| 18752142 | 2008 | |||||
| 23631430 | 2013 | |||||
| 24667783 | 2015 | |||||
| 26940925 | 2016 | |||||
| 20129283 | 2010 | |||||
| 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 | 8 | V1328M, |
| 1340 | 14 | V1340I, |
| 1757 | 13 | |
| 1472 | 10 | p.N1472del, N1472S, |
| 1339 | 12 | L1339F, p.L1339del, |
| 1333 | 4 | |
| 1471 | 13 | |
| 1762 | 12 | p.I1762del, I1762M, |
| 1464 | 14 | c.4389_4396delCCTCTTTA, L1464P, |
| 944 | 14 | |
| 1329 | 5 | G1329S, |
| 1766 | 14 | M1766L, M1766V, M1766L, M1766T |
| 1334 | 6 | I1334V, |
| 1473 | 14 | F1473S, F1473C, |
| 1341 | 15 | |
| 1468 | 10 | V1468F, V1468A, |
| 1324 | 13 | |
| 1327 | 9 | |
| 1758 | 14 | I1758V, p.I1758del, |
| 1330 | 5 | A1330T, A1330P, A1330D, |
| 1338 | 10 | L1338V, |
| 1337 | 10 | |
| 1326 | 10 | A1326S, |
| 1332 | 0 | P1332Q, P1332L, |
| 1465 | 12 | p.F1465_L1480dup, |
| 1467 | 14 | |
| 1476 | 14 | Q1476X, Q1476R, |
| 1331 | 4 | I1331V, |
| 1761 | 14 | c.5280delG, L1761F, L1761H, |
| 1475 | 14 | p.Q1475NfsX6, Q1475L, |
| 1469 | 12 | I1469V, |
| 1336 | 7 | |
| 824 | 13 | |
| 1325 | 12 | N1325S, |
| 1335 | 5 | M1335R, |