SCN5A Variant p.E429del

Summary of observed carriers, functional annotations, and structural context for SCN5A p.E429del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

21%

1/13 effective observations

Estimated BrS1 penetrance

10%

1/13 effective observations

Total carriers

3

0 BrS1 · 1 LQT3 · 2 unaffected

p.E429del is present in 2 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_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 None 10 14

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
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD 3 2 1 0
Variant features alone 15 14 0 1

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)
19716085 2009

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 p.E429del.
Neighbour residue Distance (Å) Observed variants
414 15 M414V,
415 14 A415T,
416 14 Y416C,
417 13
418 13 E418K,
419 12 Q419X,
420 11
421 11
422 10
423 9
424 8 I424M,
425 8 A425T, A425P,
426 7
427 5
428 4 E428K,
429 0 E429K, p.E429del,
430 4 K430E,
431 5
432 7
433 8 R433S, R433C, R433H,
434 8
435 9
436 10
437 11 A437V,
438 11 M438L, M438L, M438T,
439 12 E439K, E439V,
440 13
441 13 L441F,
442 14
443 14
444 15 E444fsX14