KCNH2 Variant A142T

Summary of observed carriers, functional annotations, and structural context for KCNH2 A142T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

6%

0/13 effective observations

Total carriers

3

0 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

A142T is present in 3 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 121% of WT with a standard error of 21%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-0.456 0.0 2 0.349 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 LQT2 Other Disease
Literature, cohort, and gnomAD – 3 2 0 –
Variant features alone – 10 10 0 –

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 A142T.
Neighbour residue Distance (Å) Observed variants
142 0 A142T,
141 4 P141fsX, P141S, P141L,
143 4
140 5 S140Y,
144 5 D144V,
139 7 G139R, G139A, G139R,
145 7
138 8
146 8 N146X,
137 8
147 8 H147R, H147X,
136 9
148 9 R148fsX, R148Q, R148Y, R148W,
135 10
149 10 G149V, G149A,
134 11 E134X,
150 11 P150L,
133 11 M133T,
151 11 P151fsX, P151X,
132 12 V132X,
152 12 T152S, T152S, T152I, T152X, T152fsX,
131 13 V131fsX, V131L, V131L,
153 13 S153R, S153R, S153R,
130 13 E130K,
154 13 W154R, W154X, W154R,
129 14 F129C,
155 14
128 14 N128S,
156 14
127 15
157 15 P157X,