KCNQ1 Variant P641L

Summary of observed carriers, functional annotations, and structural context for KCNQ1 P641L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

9%

1/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

P641L is present in 1 alleles in gnomAD. This residue resides in a Non_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 (%)
-1.45 0.008 -3 0.513 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 9 1 –

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 P641L.
Neighbour residue Distance (Å) Observed variants
641 0 P641L,
640 4 Q640L,
642 4
639 5
643 5 G643S,
638 7
644 7
637 8
645 8
636 8
646 8 G646S
635 9 G635R, G635R,
647 9
634 10
648 10 V648I,
633 11
649 11 D649N, D649G,
632 11
650 11
631 12 P631R,
651 12
630 13 P630S, P630T,
652 13
629 13 G629S,
653 13 F653Y,
628 14 G628S, G628D,
654 14
627 14
655 14
626 15 G626S,
656 15