KCNQ1 Variant D603H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D603H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

34%

3/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

D603H has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
-4.33	1.0	-1	0.927	38

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	7	3	–

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 D603H.
Neighbour residue	Distance (Å)	Observed variants
603	0
602	4
604	4
601	5
605	5
600	7	T600M,
606	7
599	8
607	8	A607T,
598	8	K598R,
608	8
597	9
609	9
596	10	E596del, E596K,
610	10
595	11	V595L, V595L
611	11	D611N, D611Y,
594	11	R594Q, R594P,
612	11
593	12	N593S,
613	12
592	13
614	13	H614del,
591	13	R591H, R591C, R591L,
615	13
590	14	A590T,
616	14
589	14	G589D, G589S,
617	14
588	15	I588F,
618	15