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

G386E has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
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.

Previously observed variants near G386E.
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