KCNQ1 Variant D649Y

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D649Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

0/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

D649Y has not been reported 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 (%)
-0.85	0.0	2	0.567	0

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	–	0	0	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 D649Y.
Neighbour residue	Distance (Å)	Observed variants
649	0	D649N, D649G,
648	4	V648I,
650	4
647	5
651	5
646	7	G646S
652	7
645	8
653	8	F653Y,
644	8
654	8
643	9	G643S,
655	9
642	10
656	10
641	11	P641L,
657	11	N657S,
640	11	Q640L,
658	11	T658N,
639	12
659	12
638	13
660	13	P660S,
637	13
661	13
636	14
662	14
635	14	G635R, G635R,
663	14	E663K,
634	15
664	15