SCN5A Variant L1222R
Summary of observed carriers, functional annotations, and structural context for SCN5A L1222R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
47%
2/11 effective observations
Estimated BrS1 penetrance
15%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.82 | 0.926 | -5.27 | 0.946 | 14 | 51 |
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 | 13 | 1 | 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) |
|---|---|---|---|---|---|---|
| 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 |
|---|---|---|
| 1245 | 13 | M1245I, |
| 1218 | 6 | S1218I, S1218T, |
| 1281 | 14 | c.3840+1G>A, V1281F, |
| 1304 | 8 | T1304M, |
| 1217 | 9 | |
| 1243 | 10 | D1243N, |
| 1216 | 10 | L1216V, |
| 1234 | 14 | |
| 1698 | 14 | A1698T, |
| 1285 | 15 | |
| 1299 | 15 | c.3894delC, |
| 1220 | 5 | G1220E, |
| 1673 | 7 | |
| 1675 | 12 | |
| 1213 | 14 | |
| 1241 | 13 | |
| 1309 | 13 | R1309H, R1309C, |
| 1226 | 8 | |
| 1669 | 9 | |
| 1671 | 14 | |
| 1221 | 4 | A1221V, |
| 1242 | 9 | |
| 1668 | 15 | M1668T, |
| 1676 | 10 | M1676T, M1676I, |
| 1219 | 5 | S1219N, |
| 1672 | 10 | S1672Y |
| 1239 | 7 | L1239P, |
| 1310 | 12 | |
| 1306 | 8 | R1306H, R1306S, |
| 1665 | 14 | |
| 1305 | 11 | |
| 1246 | 11 | |
| 1235 | 10 | |
| 1282 | 14 | S1282A, |
| 1302 | 12 | p.L1302Vfs18, |
| 1247 | 14 | T1247I, |
| 1237 | 14 | V1237F, |
| 1701 | 14 | M1701I, |
| 1307 | 8 | |
| 1228 | 13 | Y1228C, Y1228H, Y1228F, |
| 1678 | 14 | N1678S, |
| 1223 | 5 | c.3667delG, |
| 1697 | 10 | |
| 1222 | 0 | L1222R, p.L1222LfsX7, |
| 1227 | 13 | |
| 1300 | 15 | |
| 1674 | 12 | F1674V, |
| 1229 | 11 | |
| 1215 | 10 | I1215V, |
| 1301 | 10 | |
| 1214 | 13 | M1214T, |
| 1696 | 12 | |
| 1700 | 14 | |
| 1677 | 11 | |
| 1308 | 12 | L1308F, |
| 1250 | 14 | |
| 1224 | 7 | |
| 1670 | 11 | |
| 1240 | 11 | E1240Q, |
| 1225 | 6 | E1225K, G1225K, |
| 1278 | 13 | I1278N, |
| 1238 | 11 | |
| 1236 | 13 | K1236R, K1236N, |
| 1303 | 7 | R1303W, R1303Q, |
| 1666 | 13 |