KCNQ1 Variant G626S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 G626S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

36%

5/15 effective observations

Total carriers

5

3 LQT1 · 2 unaffected

Functional studies

1

Publications with functional data

G626S is present in 2 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.07 0.079 0 0.566 35

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
19322600 2009 2 None 1 None
16922724 2006 1 None 1 None
Literature, cohort, and gnomAD – 5 2 3 –
Variant features alone – 15 8 2 –

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 G626S.
Neighbour residue Distance (Å) Observed variants
626 0 G626S,
625 4 P625R,
627 4
624 5
628 5 G628S, G628D,
623 7
629 7 G629S,
622 8 G622S,
630 8 P630S, P630T,
621 8 G621S, G621C, G621D,
631 8 P631R,
620 9
632 9
619 10 L619M,
633 10
618 11
634 11
617 11
635 11 G635R, G635R,
616 12
636 12
615 13
637 13
614 13 H614del,
638 13
613 14
639 14
612 14
640 14 Q640L
611 15 D611N, D611Y,
641 15 P641L,