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 |