SCN5A Variant I424S

Summary of observed carriers, functional annotations, and structural context for SCN5A I424S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

30%

1/10 effective observations

Estimated BrS1 penetrance

8%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I424S has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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 0.766 2 39

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 I424S.
Neighbour residue Distance (Å) Observed variants
409 15 L409V, L409P,
410 14 A410V,
411 14 V411M,
412 13 V412D,
413 13 A413E, A413T,
414 12 M414V,
415 11 A415T,
416 11 Y416C,
417 10
418 9 E418K,
419 8 Q419X,
420 8
421 7
422 5
423 4
424 0 I424M,
425 4 A425T, A425P,
426 5
427 7
428 8 E428K,
429 8 E429K, p.E429del,
430 9 K430E,
431 10
432 11
433 11 R433C, R433H, R433S,
434 12
435 13
436 13
437 14 A437V,
438 14 M438T, M438L, M438L,
439 15 E439V, E439K,