KCNQ1 Variant L425V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L425V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

10%

1/12 effective observations

Total carriers

2

0 LQT1 · 2 unaffected

Functional studies

0

Publications with functional data

L425V is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.58 0.001 -2 0.502 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. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT1 Other Disease
Literature, cohort, and gnomAD – 2 2 0 –
Variant features alone – 15 9 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 L425V.
Neighbour residue Distance (Å) Observed variants
425 0 L425V,
424 4 K424T,
426 4
423 5
427 5
422 7 K422T, K422R,
428 7 D428G,
421 8 K421N, K421N,
429 8 N429S,
420 8 K420E, K420N, K420N,
430 8
419 9
431 9 V431L, V431L,
418 10 V418I,
432 10 T432I, T432A
417 11 V417M,
433 11 P433A,
416 11 V416M,
434 11 G434R, G434R,
415 12
435 12
414 13
436 13
413 13 K413R,
437 13 M437V,
412 14 P412S,
438 14
411 14
439 14
410 15
440 15