KCNQ1 Variant K557E

Summary of observed carriers, functional annotations, and structural context for KCNQ1 K557E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

62%

11/19 effective observations

Total carriers

9

5 LQT1 · 4 unaffected

Functional studies

2

Publications with functional data

K557E has not been reported 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 (%)
-3.48 1.0 0 0.949 69

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
25139741 2014 8 4 4 None
19716085 2009 1 None 1 None
Literature, cohort, and gnomAD 9 4 5
Variant features alone 15 4 6

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

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 K557E.
Neighbour residue Distance (Å) Observed variants
561 11
556 12
562 13 R562M, R562S, R562S,
559 13 L559P
560 14
552 14 L552F,
563 14
553 14
564 15 D564H, D564N,
557 15 K557E,