KCNQ1 Variant R243C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R243C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

76%

18/25 effective observations

Total carriers

15

12 LQT1 · unaffected

Functional studies

3

Publications with functional data

R243C is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 6 individuals with LQT1 and 4 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-7.78 1.0 -4 0.961 78

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 8 None 8 None
30758498 2019 9 None 5 None
29672598 2018 1 1 None Epilepsy
26496715 2016 2 None 2 None
23153844 2012 13 None 1 None
22949429 2012 2 None 2 None
21131640 2011 1 None 1 None
20167303 2010 3 1 1 Epilepsy in 1
19934648 2010 None None None None
19841300 2009 2 None 2 None
19716085 2009 1 None 1 None
19490272 2009 13 None 13 None
18713323 2008 13 None None None
17470695 2007 13 None 13 None
17192539 2006 1 None 1 None
15469540 2004 2 None 1 None
14678125 2003 1 None 1 None
12877697 2003 1 1 None None
Literature, cohort, and gnomAD – 15 12 –
Variant features alone – 15 4 6 –

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