KCNQ1 Variant A128D

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A128D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

69%

6/10 effective observations

Total carriers

0

0 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

A128D has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-1.9 0.083 -4 0.682 76

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 4 6 –

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 A128D.
Neighbour residue Distance (Å) Observed variants
128 0 A128del,
129 4 V129I,
127 5 F127L, F127L, F127L,
131 5
132 6 I132L,
124 6
125 6
126 7 H126D,
130 7
123 8
133 8 V133I,
134 9 L134P,
135 10
241 10 V241F, V241I, V241G
122 11 C122Y,
166 11 F166V,
121 11
163 12
120 12 W120C, W120C,
167 12
113 12
136 12
170 12
238 13 M238V, M238L, M238L,
240 13 H240R, H240P,
114 13
237 13
159 13 M159del,
137 14 L137F, L137P,
119 14 G119R, G119V,
117 14 P117L,
243 14 R243H, R243C, R243P, R243S,
138 14
162 14 V162M,
139 15