SCN5A Variant E1240Q
Summary of observed carriers, functional annotations, and structural context for SCN5A E1240Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/21 effective observations
Estimated BrS1 penetrance
13%
2/21 effective observations
Total carriers
11
1 BrS1 · 0 LQT3 · 10 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.75 | 0.95 | 1.76 | 0.928 | 19 | 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 |
|---|---|---|---|---|---|---|---|
| 11901046 | 2002 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 11 | 10 | 0 | 1 | – | |
| Variant features alone | – | 15 | 14 | 0 | 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.
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, |
| 1233 | 11 | K1233E, |
| 1218 | 12 | S1218T, S1218I, |
| 1281 | 14 | c.3840+1G>A, V1281F, |
| 1304 | 13 | T1304M, |
| 1217 | 15 | |
| 1243 | 5 | D1243N, |
| 1234 | 11 | |
| 1285 | 9 | |
| 1299 | 11 | c.3894delC, |
| 1220 | 14 | G1220E, |
| 1298 | 13 | P1298L, |
| 1283 | 14 | L1283M, |
| 1241 | 7 | |
| 1226 | 13 | |
| 1288 | 12 | A1288G, |
| 1221 | 11 | A1221V, |
| 1242 | 6 | |
| 1219 | 14 | S1219N, |
| 1239 | 5 | L1239P, |
| 1306 | 12 | R1306H, R1306S, |
| 1244 | 8 | K1244E, |
| 1286 | 11 | |
| 1282 | 12 | S1282A, |
| 1235 | 9 | |
| 1246 | 11 | |
| 1302 | 13 | p.L1302Vfs18, |
| 1247 | 11 | T1247I, |
| 1237 | 6 | V1237F, |
| 1289 | 9 | |
| 1223 | 14 | c.3667delG, |
| 1222 | 11 | p.L1222LfsX7, L1222R, |
| 1230 | 12 | E1230K, |
| 1300 | 14 | |
| 1229 | 10 | |
| 1301 | 12 | |
| 1292 | 14 | |
| 1284 | 13 | |
| 1291 | 15 | |
| 1250 | 15 | |
| 1224 | 14 | |
| 1240 | 0 | E1240Q, |
| 1225 | 9 | E1225K, G1225K, |
| 1248 | 12 | |
| 1287 | 14 | |
| 1290 | 14 | |
| 1238 | 7 | |
| 1236 | 7 | K1236R, K1236N |
| 1249 | 15 | V1249D, |
| 1303 | 8 | R1303W, R1303Q, |