KCNQ1 Variant E596K

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E596K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

79%

8/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

E596K 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 (%)
-3.22 0.996 1 0.888 84

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 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 E596K.
Neighbour residue Distance (Å) Observed variants
596 0 E596del, E596K,
595 4 V595L, V595L
597 4
594 5 R594Q, R594P,
598 5 K598R,
593 7 N593S,
599 7
592 8
600 8 T600M,
591 8 R591H, R591C, R591L,
601 8
590 9 A590T,
602 9
589 10 G589D, G589S,
603 10
588 11 I588F,
604 11
587 11 T587M, T587R,
605 11
586 12 N586D,
606 12
585 13 S585N,
607 13 A607T,
584 13 G584S,
608 13
583 14 R583H, R583C, R583G,
609 14
582 14
610 14
581 15
611 15 D611N, D611Y,