KCNQ1 Variant G635R

Summary of observed carriers, functional annotations, and structural context for KCNQ1 G635R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

35%

5/17 effective observations

Total carriers

7

3 LQT1 · 4 unaffected

Functional studies

1

Publications with functional data

G635R is present in 4 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 (%)
-0.24 0.001 0 0.523 36

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
21956039 2011 1 None 1 None
Literature, cohort, and gnomAD – 7 4 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 G635R.
Neighbour residue Distance (Å) Observed variants
635 0 G635R, G635R,
634 4
636 4
633 5
637 5
632 7
638 7
631 8 P631R,
639 8
630 8 P630S, P630T,
640 8 Q640L,
629 9 G629S,
641 9 P641L,
628 10 G628S, G628D,
642 10
627 11
643 11 G643S,
626 11 G626S,
644 11
625 12 P625R,
645 12
624 13
646 13 G646S
623 13
647 13
622 14 G622S,
648 14 V648I,
621 14 G621S, G621C, G621D,
649 14 D649N, D649G,
620 15
650 15