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 |