SCN5A Variant G386E
Summary of observed carriers, functional annotations, and structural context for SCN5A G386E. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/12 effective observations
Estimated BrS1 penetrance
60%
7/12 effective observations
Total carriers
2
2 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.85 | 1 | -3.75 | 0.971 | 76 | 3 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 2 | 0 | 2 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 0 | 0 | 2 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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) |
|---|---|---|---|---|---|---|
| 20129283 | 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 |
|---|---|---|
| 328 | 9 | |
| 333 | 8 | c.998+5G>A, c.998+1G>A, |
| 271 | 11 | L271V, |
| 1702 | 9 | |
| 326 | 11 | |
| 276 | 11 | L276Q, L276P, |
| 387 | 5 | |
| 385 | 3 | A385T, |
| 355 | 14 | F355C, F355I, |
| 391 | 10 | |
| 330 | 8 | S330F, |
| 278 | 11 | H278R, H278D, |
| 388 | 5 | I388S, |
| 1698 | 11 | A1698T, |
| 334 | 11 | c.999-424_1338+81del, |
| 332 | 5 | A332T, |
| 327 | 9 | |
| 1706 | 14 | Q1706H, Q1706H, |
| 384 | 6 | S384T, |
| 329 | 6 | |
| 1692 | 10 | |
| 386 | 0 | G386E, G386R, G386R, |
| 1693 | 14 | |
| 378 | 9 | |
| 1699 | 11 | |
| 331 | 8 | |
| 379 | 10 | |
| 1703 | 14 | |
| 272 | 9 | |
| 341 | 14 | C341Y, |
| 274 | 13 | G274C, |
| 335 | 14 | C335S, C335S, C335R, |
| 1701 | 13 | M1701I, M1701I, M1701I, |
| 325 | 11 | L325R, |
| 1690 | 15 | D1690N, c.5068_5070delGA, |
| 392 | 11 | |
| 324 | 14 | |
| 1697 | 14 | |
| 389 | 5 | Y389X, Y389H, |
| 1620 | 13 | T1620K, T1620M, |
| 395 | 15 | |
| 393 | 10 | |
| 394 | 13 | |
| 390 | 8 | |
| 275 | 10 | N275K, N275K, |
| 383 | 8 | |
| 382 | 4 | |
| 374 | 14 | W374G, |
| 1696 | 14 | |
| 1705 | 13 | |
| 1689 | 13 | D1689N, |
| 1700 | 14 | |
| 381 | 6 | c.1140+1G>A, c.1141-3C>A, |
| 375 | 15 | |
| 1691 | 9 | |
| 380 | 11 | |
| 268 | 13 | G268S |
| 377 | 12 |