KCNQ1 Variant D540Y

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D540Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

52%

5/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

D540Y has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 5 individuals with LQT1 and 5 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
-7.84	1.0	-4	0.957	57

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	5	5	–

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 D540Y.
Neighbour residue	Distance (Å)	Observed variants
538	11
541	11	V541I,
531	12
535	12
542	12
366	13	R366W, R366Q,
540	13
537	13
533	13	R533W, R533Q,
534	13
362	13	K362R, K362del,
536	14
539	14	R539W, R539L, R539Q
361	14
529	14
527	14
547	14	Q547R,
545	14
370	14	A370V,
532	15
528	15