KCNQ1 Variant E492A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E492A. 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

E492A 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 (%)
-3.54	0.01	-1	0.699	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	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 E492A.
Neighbour residue	Distance (Å)	Observed variants
492	0	L492ins,
491	4
493	4	G493A,
490	5
494	5
489	7
495	7	T495S, T495S, T495A
488	8	D488E, D488E,
496	8
487	8	E487K,
497	8	L497P,
486	9	A486T,
498	9
485	10	F485S,
499	10	P499S,
484	11
500	11	I500L, I500V,
483	11
501	11	T501A,
482	12	T482N, T482A, T482S, T482S,
502	12
481	13
503	13
480	13	M480T,
504	13
479	14	F479L, F479L, F479L,
505	14	Q505R,
478	14	H478Y,
506	14
477	15	P477L, P477T,
507	15	R507Q, R507W,