KCNQ1 Variant E543K

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E543K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

65%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

E543K 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 (%)
-3.49 0.992 0 0.936 68

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
19716085 2009 1 None 1 None
Literature, cohort, and gnomAD 1 0 1
Variant features alone 15 4 6

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 E543K.
Neighbour residue Distance (Å) Observed variants
527 9
547 11 Q547R,
524 12 V524G,
541 13 V541I,
545 13
542 13
530 13
366 14 R366W, R366Q,
525 14 A525T, A525V,
528 14
362 14 K362R, K362del,
550 14
531 14
538 14
370 15 A370V,
532 15
543 15 E543K,
546 15 S546L, S546W
544 15 Q544E,