KCNQ1 Variant E146A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E146A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

14%

1/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

E146A 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 (%)
-4.36	0.124	0	0.729	6

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 E146A.
Neighbour residue	Distance (Å)	Observed variants
146	0	E146K, E146G, E146Q,
149	6
147	6	Q147R,
145	6
144	7	T144A,
143	7	S143F, S143P, S143Y,
148	8
150	8	A150T,
142	10
297	10	G297S, G297D, G297R,
298	10	S298I, S298N,
152	10
153	10	T153M,
151	11
141	11	V141M,
140	12	S140G, S140R, S140R, S140R,
285	12
227	13
281	13	Y281C
294	13	V294M,
231	13	R231C, R231H, R231S,
300	13	A300T, A300S,
301	14
299	14
154	14
139	14
156	14
286	15
155	15