SCN5A Variant K432E

Summary of observed carriers, functional annotations, and structural context for SCN5A K432E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/10 effective observations

Estimated BrS1 penetrance

13%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

K432E has not been reported 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 1 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 (%)
NA NA NA 0.413 13 4

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 0 0 0 0
Variant features alone 15 14 0 1

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 K432E.
Neighbour residue Distance (Å) Observed variants
417 15
418 14 E418K,
419 14 Q419X,
420 13
421 13
422 12
423 11
424 11 I424M,
425 10 A425T, A425P,
426 9
427 8
428 8 E428K,
429 7 E429K, p.E429del,
430 5 K430E,
431 4
432 0
433 4 R433S, R433C, R433H,
434 5
435 7
436 8
437 8 A437V,
438 9 M438L, M438L, M438T,
439 10 E439K, E439V,
440 11
441 11 L441F,
442 12
443 13
444 13 E444fsX14,
445 14 H445D, H445Y, H445Q, H445Q,
446 14 E446K,
447 15 c.1338+2T>A, c.1339-24G>A, A447S, A447G