SCN5A Variant E439V

Summary of observed carriers, functional annotations, and structural context for SCN5A E439V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

31%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E439V is present in 1 alleles 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 3 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 (%)
-6.75 0.998 -3.75 0.883 44 0

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
Literature, cohort, and gnomAD 1 1 0 0
Variant features alone 15 12 0 3

Totals may differ from individual publications due to duplicate patients removed during curation.

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 E439V.
Neighbour residue Distance (Å) Observed variants
424 15 I424M,
425 14 A425T, A425P,
426 14
427 13
428 13 E428K,
429 12 E429K, p.E429del,
430 11 K430E,
431 11
432 10
433 9 R433S, R433C, R433H,
434 8
435 8
436 7
437 5 A437V,
438 4 M438L, M438L, M438T,
439 0 E439K, E439V,
440 4
441 5 L441F,
442 7
443 8
444 8 E444fsX14,
445 9 H445D, H445Y, H445Q, H445Q,
446 10 E446K,
447 11 c.1338+2T>A, c.1339-24G>A, A447S, A447G,
448 11
449 12 T449A, Y449C,
450 13
451 13
452 14 G452D,
453 14 V453M
454 15