KCNQ1 Variant G621D

Summary of observed carriers, functional annotations, and structural context for KCNQ1 G621D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

32%

3/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

G621D has not been reported 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 (%)
0.64 0.0 -1 0.629 33

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 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 8 2 –

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 G621D.
Neighbour residue Distance (Å) Observed variants
621 0 G621S, G621C, G621D,
620 4
622 4 G622S,
619 5 L619M,
623 5
618 7
624 7
617 8
625 8 P625R,
616 8
626 8 G626S,
615 9
627 9
614 10 H614del,
628 10 G628S, G628D,
613 11
629 11 G629S,
612 11
630 11 P630S, P630T
611 12 D611N, D611Y,
631 12 P631R,
610 13
632 13
609 13
633 13
608 14
634 14
607 14 A607T,
635 14 G635R, G635R,
606 15
636 15