SCN5A Variant K1236R
Summary of observed carriers, functional annotations, and structural context for SCN5A K1236R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/12 effective observations
Estimated BrS1 penetrance
40%
4/12 effective observations
Total carriers
2
1 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.15 | 0.571 | 2.92 | 0.755 | 60 | 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 |
|---|---|---|---|---|---|---|---|
| 21126620 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 1 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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) |
|---|---|---|---|---|---|---|
| 21126620 | 2010 |
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 | 5 | K1233E, |
| 1243 | 12 | D1243N, |
| 1234 | 7 | |
| 1285 | 15 | |
| 1299 | 13 | c.3894delC, |
| 1298 | 14 | P1298L, |
| 1241 | 12 | |
| 1226 | 11 | |
| 1221 | 13 | A1221V, |
| 1242 | 11 | |
| 1239 | 7 | L1239P, |
| 1244 | 14 | K1244E, |
| 1235 | 6 | |
| 1231 | 10 | E1231K, |
| 1237 | 5 | V1237F, |
| 1289 | 14 | |
| 1228 | 12 | Y1228H, Y1228F, Y1228C, |
| 1223 | 14 | c.3667delG, |
| 1222 | 13 | p.L1222LfsX7, L1222R, |
| 1230 | 6 | E1230K, |
| 1227 | 12 | |
| 1229 | 5 | |
| 1301 | 14 | |
| 1224 | 13 | |
| 1240 | 7 | E1240Q, |
| 1225 | 8 | E1225K, G1225K, |
| 1232 | 11 | R1232Q, R1232W, |
| 1238 | 8 | |
| 1236 | 0 | K1236N, K1236R, K1236N, |
| 1303 | 12 | R1303Q, R1303W, |