KCNH2 Variant D144V

Summary of observed carriers, functional annotations, and structural context for KCNH2 D144V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

2%

0/32 effective observations

Total carriers

22

0 LQT2 · 13 unaffected

Functional studies

0

Publications with functional data

D144V is present in 22 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 97% of WT with a standard error of 17%. 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 (%)
-1.454 0.937 -2 0.464 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 – 22 13 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 D144V.
Neighbour residue Distance (Å) Observed variants
144 0 D144V,
143 4
145 4
142 5 A142T,
146 5 N146X,
141 7 P141fsX, P141L, P141S,
147 7 H147R, H147X,
140 8 S140Y,
148 8 R148Q, R148fsX, R148W, R148Y,
139 8 G139R, G139R, G139A,
149 8 G149V, G149A,
138 9
150 9 P150L,
137 10
151 10 P151X, P151fsX,
136 11
152 11 T152I, T152X, T152fsX, T152S, T152S,
135 11
153 11 S153R, S153R, S153R,
134 12 E134X,
154 12 W154R, W154R, W154X,
133 13 M133T,
155 13
132 13 V132X,
156 13
131 14 V131L, V131fsX, V131L,
157 14 P157X,
130 14 E130K,
158 14
129 15 F129C,
159 15