KCNQ1 Variant A46T

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A46T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

32%

6/20 effective observations

Total carriers

10

5 LQT1 · unaffected

Functional studies

1

Publications with functional data

A46T is present in 1 alleles in gnomAD. This residue resides in a Mild_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 (%)
-0.2 0.0 1 0.522 25

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
26423924 2016 3 3 None 1 SUDEP
25786344 2015 1 1 None None
24144883 2014 1 None None Early onset AF
23631430 2013 2 None None None
21956039 2011 2 None 2 None
19808498 2009 1 None 1 None
19716085 2009 2 None 2 None
Literature, cohort, and gnomAD 10 5
Variant features alone 15 9 1

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