SCN5A Variant D1243N
Summary of observed carriers, functional annotations, and structural context for SCN5A D1243N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/57 effective observations
Estimated BrS1 penetrance
10%
5/57 effective observations
Total carriers
47
5 BrS1 · 0 LQT3 · 42 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.89 | 1 | 4.97 | 0.924 | 11 | 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 |
|---|---|---|---|---|---|---|---|
| 22885917 | 2012 | 2 | 0 | 2 | 0 | ||
| 26173111 | 2015 | 1 | 0 | 1 | 0 | ||
| 26921764 | 2016 | 2 | 0 | 2 | 0 | ||
| 26746457 | 2016 | 1 | 0 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 5 | 0 | 5 | 0 | ||
| 29325976 | 2018 | 3 | 0 | 3 | 0 | ||
| Literature, cohort, and gnomAD | – | 47 | 42 | 0 | 5 | – | |
| Variant features alone | – | 15 | 15 | 0 | 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) |
|---|---|---|---|---|---|---|
| 22885917 | 2012 | |||||
| 26173111 | 2015 | |||||
| 26921764 | 2016 | |||||
| 26746457 | 2016 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 29325976 | 2018 | |||||
| 32533946 | 2020 | HEK | 115 | 5.7 | 7.8 |
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 | 7 | M1245I, M1245I, M1245I, |
| 1218 | 10 | S1218T, S1218I, |
| 1281 | 10 | c.3840+1G>A, V1281F, |
| 1304 | 11 | T1304M, |
| 1217 | 13 | |
| 1243 | 0 | D1243N, |
| 1285 | 7 | |
| 1299 | 11 | c.3894delC, |
| 1220 | 13 | G1220E, |
| 1673 | 15 | |
| 1298 | 15 | P1298L, |
| 1283 | 10 | L1283M, |
| 1241 | 8 | |
| 1309 | 14 | R1309C, R1309H |
| 1226 | 15 | |
| 1288 | 11 | A1288G, |
| 1221 | 11 | A1221V, |
| 1242 | 5 | |
| 1219 | 12 | S1219N, |
| 1251 | 12 | V1251M, |
| 1279 | 11 | V1279I, |
| 1239 | 7 | L1239P, |
| 1306 | 7 | R1306S, R1306H, |
| 1244 | 6 | K1244E, |
| 1286 | 8 | |
| 1305 | 12 | |
| 1282 | 7 | S1282A, |
| 1246 | 7 | |
| 1235 | 12 | |
| 1302 | 10 | p.L1302Vfs18, |
| 1247 | 6 | T1247I, |
| 1237 | 11 | V1237F, |
| 1307 | 13 | |
| 1289 | 9 | |
| 1223 | 15 | c.3667delG, |
| 1222 | 10 | p.L1222LfsX7, L1222R, |
| 1300 | 14 | |
| 1229 | 14 | |
| 1215 | 13 | I1215V, |
| 1301 | 11 | |
| 1214 | 13 | M1214T, |
| 1253 | 15 | E1253G, |
| 1284 | 10 | |
| 1280 | 13 | |
| 1250 | 9 | |
| 1240 | 5 | E1240Q, |
| 1248 | 9 | |
| 1225 | 11 | E1225K, G1225K, |
| 1287 | 12 | |
| 1290 | 14 | |
| 1278 | 11 | I1278N, |
| 1238 | 10 | |
| 1236 | 12 | K1236R, K1236N, K1236N, |
| 1249 | 10 | V1249D, |
| 1303 | 6 | R1303W, R1303Q, |