SCN5A Variant A425S

Summary of observed carriers, functional annotations, and structural context for SCN5A A425S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

31%

1/10 effective observations

Estimated BrS1 penetrance

7%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

A425S has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 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 0.53 2 41

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 1 0 – –

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 A425S.
Neighbour residue Distance (Å) Observed variants
410 15 A410V,
411 14 V411M,
412 14 V412D,
413 13 A413T, A413E,
414 13 M414V,
415 12 A415T,
416 11 Y416C,
417 11
418 10 E418K,
419 9 Q419X,
420 8
421 8
422 7
423 5
424 4 I424M,
425 0 A425T, A425P,
426 4
427 5
428 7 E428K,
429 8 E429K, p.E429del,
430 8 K430E,
431 9
432 10
433 11 R433S, R433C, R433H,
434 11
435 12
436 13
437 13 A437V,
438 14 M438L, M438L, M438T,
439 14 E439K, E439V
440 15