SCN5A Variant L1239P
Summary of observed carriers, functional annotations, and structural context for SCN5A L1239P. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/12 effective observations
Estimated BrS1 penetrance
35%
4/12 effective observations
Total carriers
2
1 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -6.84 | 1 | -5.59 | 0.996 | 39 | 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 | – | 2 | 1 | 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 |
|---|---|---|
| 1245 | 10 | M1245I, M1245I, M1245I, |
| 1233 | 11 | K1233E, |
| 1218 | 9 | S1218T, S1218I, |
| 1304 | 12 | T1304M, |
| 1217 | 11 | |
| 1243 | 7 | D1243N, |
| 1216 | 15 | L1216V, |
| 1234 | 9 | |
| 1285 | 13 | |
| 1299 | 14 | c.3894delC, |
| 1220 | 10 | G1220E, |
| 1673 | 13 | |
| 1241 | 8 | |
| 1226 | 10 | |
| 1221 | 6 | A1221V, |
| 1242 | 6 | |
| 1676 | 14 | M1676T, M1676I, M1676I, M1676I |
| 1219 | 10 | S1219N, |
| 1239 | 0 | L1239P, |
| 1306 | 11 | R1306S, R1306H, |
| 1244 | 11 | K1244E, |
| 1282 | 14 | S1282A, |
| 1246 | 10 | |
| 1235 | 5 | |
| 1302 | 14 | p.L1302Vfs18, |
| 1231 | 14 | E1231K, |
| 1247 | 13 | T1247I, |
| 1237 | 7 | V1237F, |
| 1307 | 14 | |
| 1289 | 14 | |
| 1228 | 13 | Y1228H, Y1228C, Y1228F, |
| 1223 | 10 | c.3667delG, |
| 1697 | 15 | |
| 1222 | 7 | p.L1222LfsX7, L1222R, |
| 1230 | 12 | E1230K, |
| 1227 | 13 | |
| 1229 | 8 | |
| 1215 | 14 | I1215V, |
| 1301 | 12 | |
| 1214 | 14 | M1214T, |
| 1677 | 14 | |
| 1250 | 15 | |
| 1224 | 9 | |
| 1240 | 5 | E1240Q, |
| 1248 | 15 | |
| 1225 | 6 | E1225K, G1225K, |
| 1232 | 14 | R1232W, R1232Q, |
| 1238 | 5 | |
| 1236 | 7 | K1236R, K1236N, K1236N, |
| 1303 | 8 | R1303W, R1303Q, |