KCNQ1 Variant A223D

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A223D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

42%

4/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

A223D has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
-5.73	1.0	-2	0.921	46

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	6	4	–

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 A223D.
Neighbour residue	Distance (Å)	Observed variants
223	0
224	4	T224M,
222	4
227	5
219	6	G219E,
221	6
220	6	Q220K,
225	6	S225L, S225del,
226	6	A226V,
228	8
215	9	V215M, V215G, V215L, V215L
217	9
216	9	G216R,
212	9
218	9
229	10	G229D,
230	11
231	12	R231C, R231H, R231S,
213	12
211	12
285	13
214	13	C214Y,
153	13	T153M,
282	14	L282P,
286	14
157	14	F157C,
208	14	A208V,
209	14	S209P,
144	14	T144A,
143	14	S143F, S143P, S143Y,
233	15	L233P,