KCNQ1 Variant D488H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D488H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

11%

1/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

D488H has not been reported 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 (%)
-3.09	0.953	0	0.788	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	–	0	0	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 D488H.
Neighbour residue	Distance (Å)	Observed variants
488	0	D488E, D488E,
487	4	E487K,
489	4
486	5	A486T,
490	5
485	7	F485S,
491	7
484	8
492	8	L492ins,
483	8
493	8	G493A,
482	9	T482N, T482A, T482S, T482S,
494	9
481	10
495	10	T495S, T495S, T495A
480	11	M480T,
496	11
479	11	F479L, F479L, F479L,
497	11	L497P,
478	12	H478Y,
498	12
477	13	P477L, P477T,
499	13	P499S,
476	13	M476L, M476L, M476V,
500	13	I500L, I500V,
475	14
501	14	T501A,
474	14
502	14
473	15	E473Q,
503	15