SCN5A Variant G1225K
Summary of observed carriers, functional annotations, and structural context for SCN5A G1225K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
8%
0/11 effective observations
Estimated BrS1 penetrance
53%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | -2.67 | None | 72 | 8 |
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 |
|---|---|---|---|---|---|---|---|
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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) |
|---|---|---|---|---|---|---|
| 29325976 | 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 |
|---|---|---|
| 1233 | 12 | K1233E, |
| 1218 | 11 | S1218T, S1218I, |
| 1304 | 10 | T1304M, |
| 1217 | 14 | |
| 1243 | 11 | D1243N, |
| 1234 | 11 | |
| 1698 | 14 | A1698T |
| 1285 | 15 | |
| 1299 | 13 | c.3894delC, |
| 1220 | 10 | G1220E, |
| 1673 | 8 | |
| 1675 | 12 | |
| 1681 | 13 | c.5040_5042delTTAinsC, Y1681F, |
| 1694 | 14 | |
| 1241 | 14 | |
| 1226 | 4 | |
| 1695 | 12 | Q1695X, |
| 1669 | 12 | |
| 1221 | 7 | A1221V, |
| 1242 | 11 | |
| 1676 | 8 | M1676T, M1676I, M1676I, M1676I, |
| 1219 | 10 | S1219N, |
| 1672 | 11 | S1672Y, |
| 1699 | 15 | |
| 1239 | 6 | L1239P, |
| 1306 | 12 | R1306S, R1306H, |
| 1305 | 14 | |
| 1680 | 12 | A1680T, A1680P, |
| 1246 | 14 | |
| 1235 | 7 | |
| 1302 | 13 | p.L1302Vfs18, |
| 1231 | 12 | E1231K, |
| 1237 | 11 | V1237F, |
| 1307 | 13 | |
| 1228 | 9 | Y1228H, Y1228C, Y1228F, |
| 1678 | 13 | N1678S, |
| 1223 | 7 | c.3667delG, |
| 1697 | 10 | |
| 1222 | 6 | p.L1222LfsX7, L1222R, |
| 1230 | 10 | E1230K, |
| 1227 | 8 | |
| 1300 | 13 | |
| 1674 | 13 | F1674V, |
| 1229 | 6 | |
| 1301 | 9 | |
| 1696 | 10 | |
| 1700 | 13 | |
| 1677 | 9 | |
| 1224 | 7 | |
| 1670 | 14 | |
| 1240 | 9 | E1240Q, |
| 1225 | 0 | E1225K, G1225K, |
| 1232 | 15 | R1232W, R1232Q, |
| 1238 | 11 | |
| 1679 | 14 | |
| 1236 | 8 | K1236R, K1236N, K1236N, |
| 1303 | 8 | R1303W, R1303Q, |