KCNQ1 Variant S349W

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S349W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

84%

10/12 effective observations

Total carriers

2

2 LQT1 · unaffected

Functional studies

1

Publications with functional data

S349W has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 8 individuals with LQT1 and 2 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.49 1.0 -4 0.95 93

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
33614747 2021 1 None 1 None
25471708 2015 1 None None JLNS w/ vestibular DFx
23153844 2012 15 None 1 None
22539601 2012 1 None None None
20662986 2011 None None None None
19490272 2009 15 None 15 None
17470695 2007 15 None 15 None
14678125 2003 10 None 10 None
Literature, cohort, and gnomAD 2 2
Variant features alone 15 2 8

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