SCN5A Variant Q245K
Summary of observed carriers, functional annotations, and structural context for SCN5A Q245K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
52%
5/15 effective observations
Estimated BrS1 penetrance
5%
0/15 effective observations
Total carriers
5
0 BrS1 · 3 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.4 | 0.953 | 2.39 | 0.906 | 1 | 56 |
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 |
|---|---|---|---|---|---|---|---|
| 15840476 | 2005 | 1 | 1 | 0 | 0 | ||
| 27566755 | 2016 | 3 | 3 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 2 | 3 | 0 | – | |
| Variant features alone | – | 15 | 13 | 2 | 0 | – | – |
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.
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 |
|---|---|---|
| 414 | 9 | M414V, |
| 249 | 5 | K249X, |
| 247 | 7 | V247L, V247L, |
| 240 | 9 | V240M, |
| 254 | 14 | |
| 193 | 14 | W193R, W193R, W193X, |
| 418 | 8 | E418K, |
| 250 | 9 | |
| 409 | 14 | L409V, L409P, |
| 237 | 12 | |
| 928 | 15 | L928P, |
| 925 | 14 | I925F, |
| 417 | 12 | |
| 933 | 12 | |
| 246 | 5 | |
| 1779 | 14 | T1779M |
| 412 | 9 | V412D, |
| 924 | 15 | V924I, |
| 245 | 0 | Q245K, |
| 244 | 5 | |
| 415 | 6 | A415T, |
| 420 | 13 | |
| 248 | 5 | |
| 241 | 6 | |
| 419 | 8 | Q419X, |
| 930 | 14 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 423 | 14 | |
| 239 | 11 | I239V, I239V , |
| 251 | 11 | |
| 410 | 13 | A410V, |
| 242 | 6 | A242D, |
| 929 | 11 | |
| 416 | 10 | Y416C, |
| 413 | 11 | A413T, A413E, |
| 236 | 14 | |
| 408 | 13 | |
| 253 | 13 | |
| 192 | 15 | |
| 936 | 14 | |
| 238 | 11 | |
| 422 | 12 | |
| 1775 | 15 | F1775V, p.F1775LfsX15, |
| 1642 | 14 | G1642E, |
| 421 | 14 | |
| 252 | 13 | |
| 411 | 9 | V411M, |
| 243 | 7 | |
| 932 | 14 |