SCN5A Variant R1309H
Summary of observed carriers, functional annotations, and structural context for SCN5A R1309H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/16 effective observations
Estimated BrS1 penetrance
8%
1/16 effective observations
Total carriers
6
0 BrS1 · 0 LQT3 · 6 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 (%) |
|---|---|---|---|---|---|
| -4.42 | 1 | -2.96 | 0.9 | 8 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 26801742 | 2016 | 7 | 0 | 0 | 2 | abnormal ECG | |
| Literature, cohort, and gnomAD | – | 6 | 6 | 0 | 0 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 26801742 | 2016 | Oocytes | 74 | 4.5 | -6.2 | 0 |
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 |
|---|---|---|
| 1271 | 9 | W1271C, W1271C, |
| 1245 | 14 | M1245I, M1245I, M1245I, |
| 1218 | 9 | S1218T, S1218I, |
| 1281 | 12 | c.3840+1G>A, V1281F, |
| 1304 | 11 | T1304M, |
| 1217 | 12 | |
| 1243 | 14 | D1243N, |
| 1315 | 12 | |
| 1274 | 7 | |
| 1216 | 9 | L1216V, |
| 1258 | 15 | |
| 1314 | 12 | c.3940_3941delCT, |
| 1220 | 13 | G1220E, |
| 1673 | 14 | |
| 1213 | 12 | |
| 1272 | 10 | |
| 1210 | 12 | F1210S, |
| 1270 | 12 | A1270S, |
| 1252 | 13 | |
| 1283 | 15 | L1283M, |
| 1309 | 0 | R1309C, R1309H, |
| 1669 | 13 | |
| 1221 | 14 | A1221V, |
| 1242 | 14 | |
| 1219 | 10 | S1219N, |
| 1251 | 13 | V1251M, |
| 1313 | 9 | |
| 1279 | 10 | V1279I, |
| 1310 | 6 | |
| 1316 | 12 | R1316Q, R1316L |
| 1207 | 13 | |
| 1306 | 7 | R1306S, R1306H, |
| 1305 | 9 | |
| 1273 | 12 | c.3816delG, W1273C, W1273C, |
| 1246 | 10 | |
| 1282 | 12 | S1282A, |
| 1302 | 14 | p.L1302Vfs18, |
| 1247 | 12 | T1247I, |
| 1257 | 11 | |
| 1307 | 7 | |
| 1256 | 15 | |
| 1275 | 5 | D1275N, |
| 1222 | 13 | p.L1222LfsX7, L1222R, |
| 1254 | 11 | |
| 1215 | 5 | I1215V, |
| 1214 | 9 | M1214T, |
| 1212 | 8 | p.I1212del, |
| 1253 | 9 | E1253G, |
| 1211 | 8 | |
| 1312 | 9 | |
| 1280 | 13 | |
| 1311 | 8 | L1311P, |
| 1308 | 7 | L1308F, |
| 1250 | 8 | |
| 1670 | 12 | |
| 1209 | 12 | T1209R, |
| 1269 | 13 | N1269S, |
| 1276 | 12 | |
| 1278 | 7 | I1278N, |
| 1266 | 12 | |
| 1249 | 11 | V1249D, |
| 1208 | 12 | E1208K, E1208X, |
| 1277 | 10 | |
| 1303 | 13 | R1303W, R1303Q, |
| 1666 | 12 |