KCNQ1 Variant D611Y

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D611Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

29%

8/29 effective observations

Total carriers

19

7 LQT1 · 12 unaffected

Functional studies

1

Publications with functional data

D611Y is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.31 0.184 -3 0.688 26

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 2 None 2 None
30758498 2019 19 None 5 None
23153844 2012 10 None 1 None
17470695 2007 10 None 10 None
15500450 2005 11 8 3 None
12808265 2003 1 None 1 None
Literature, cohort, and gnomAD – 19 12 7 –
Variant features alone – 15 9 1 –

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 D611Y.
Neighbour residue Distance (Å) Observed variants
611 0 D611N, D611Y,
610 4
612 4
609 5
613 5
608 7
614 7 H614del,
607 8 A607T,
615 8
606 8
616 8
605 9
617 9
604 10
618 10
603 11
619 11 L619M,
602 11
620 11
601 12
621 12 G621S, G621C, G621D,
600 13 T600M,
622 13 G622S,
599 13
623 13
598 14 K598R,
624 14
597 14
625 14 P625R
596 15 E596del, E596K,
626 15 G626S,