KCNQ1 Variant Q640L

Summary of observed carriers, functional annotations, and structural context for KCNQ1 Q640L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

9%

0/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

Q640L is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 0 individuals with LQT1 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.97 0.61 -2 0.58 1

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
Literature, cohort, and gnomAD – 1 1 0 –
Variant features alone – 15 10 0 –

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 Q640L.
Neighbour residue Distance (Å) Observed variants
640 0 Q640L,
639 4
641 4 P641L,
638 5
642 5
637 7
643 7 G643S,
636 8
644 8
635 8 G635R, G635R,
645 8
634 9
646 9 G646S
633 10
647 10
632 11
648 11 V648I,
631 11 P631R,
649 11 D649N, D649G,
630 12 P630S, P630T,
650 12
629 13 G629S,
651 13
628 13 G628S, G628D,
652 13
627 14
653 14 F653Y,
626 14 G626S,
654 14
625 15 P625R,
655 15