SCN5A Variant A385T

Summary of observed carriers, functional annotations, and structural context for SCN5A A385T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

13%

1/17 effective observations

Estimated BrS1 penetrance

13%

2/17 effective observations

Total carriers

7

0 BrS1 · 1 LQT3 · 6 unaffected

A385T is present in 6 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-2.96 0.997 1.63 0.784 29 9

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
27871843 2017 1 1 0 0
Literature, cohort, and gnomAD 7 6 1 0
Variant features alone 15 13 0 2

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)
27871843 2017

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 A385T.
Neighbour residue Distance (Å) Observed variants
328 7
333 9 c.998+5G>A, c.998+1G>A,
277 13
271 9 L271V,
1702 12
326 9
276 8 L276Q, L276P,
387 8
348 14 P348A,
270 14 Q270K,
279 13
385 0 A385T,
355 12 F355C, F355I,
391 12
330 9 S330F,
278 8 H278R, H278D,
388 7 I388S,
1698 14 A1698T,
334 10 c.999-424_1338+81del,
332 6 A332T,
343 13
327 7
384 4 S384T,
354 13
329 6
1692 13
386 3 G386R, G386R, G386E,
378 10
1699 14
331 10
267 14
379 12
272 8
341 11 C341Y,
274 10 G274C,
273 13
335 13 C335S, C335S, C335R,
325 9 L325R,
392 11
324 13
389 6 Y389H, Y389X,
269 15
1620 12 T1620K, T1620M,
393 11
390 11
275 7 N275K, N275K,
383 8
280 14 C280Y,
382 6
1619 15 c.4856delC, P1619Q, P1619L,
1689 14 D1689N,
342 14
381 6 c.1140+1G>A, c.1141-3C>A,
1691 11
380 10
268 12 G268S,
377 12
1621 15
353 15 T353I,