KCNH2 Variant A169G

Summary of observed carriers, functional annotations, and structural context for KCNH2 A169G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

26%

2/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A169G has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 135% of WT with a standard error of 11%. In our analysis we used SE < 20% as 'high quality'. Approximately below 50% of WT is considered PS3 moderate and below 30% is PS3 strong.

Variant features alone are equivalent to phenotyping 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-1.554 0.014 1 0.443 92

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 LQT2 Other Disease
26496715 2015 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 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. Note that some residues appear multiple times at different distances since the functional KV11.1 channel (protein product of KCNH2/hERG) is a homotetramer and occasionally the same residue from multiple subunits is present within the 15Å window.

Previously observed variants near A169G.
Neighbour residue Distance (Å) Observed variants
169 0 A169G,
168 4
170 4 L170Ins,
167 5
171 5 L171Ins,
166 7
172 7 A172V,
165 8
173 8
164 8 R164H, R164C,
174 8
163 9
175 9 A175D, A175S, A175X,
162 10 T162X,
176 10 R176Q, R176W, R176X,
161 11
177 11 E177X,
160 11
178 11
159 12
179 12 S179W,
158 13
180 13
157 13 P157X,
181 13 R181Q, R181fsX, R181W,
156 14
182 14 S182X,
155 14
183 14 G183fsX,
154 15 W154R, W154X, W154R,
184 15 G184Del,