KCNQ1 Variant L250H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L250H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

62%

11/18 effective observations

Total carriers

8

4 LQT1 · unaffected

Functional studies

0

Publications with functional data

L250H has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 7 individuals with LQT1 and 3 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.8 0.997 0 0.958 74

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
32893267 2020 1 None 1 None
30758498 2019 4 None 2 None
29439887 2018 6 4 2 None
9799083 1998 10 None 1 None
Literature, cohort, and gnomAD – 8 4 –
Variant features alone – 15 3 7 –

Totals may differ from individual publications due to duplicate patients removed during curation.