KCNQ1 Variant S566F

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S566F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

86%

13/16 effective observations

Total carriers

6

6 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

S566F 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 (%)
-2.94 0.997 3 0.83 88

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 5 None 5 None
23631430 2013 2 None None None
22949429 2012 1 None 1 None
21131640 2011 1 None 1 None
19841300 2009 1 None 1 None
19716085 2009 5 None 5 None
17470695 2007 3 None 3 None
14678125 2003 2 None 2 None
Literature, cohort, and gnomAD 6 0 6
Variant features alone 15 3 7

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 S566F.
Neighbour residue Distance (Å) Observed variants
567 8 I567T, I567S,
563 9
566 9 S566F, S566Y, S566P
564 12 D564H, D564N,
562 13 R562M, R562S, R562S,
565 14
559 14 L559P,
560 15