KCNH2 Variant G139R

Summary of observed carriers, functional annotations, and structural context for KCNH2 G139R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

5%

0/16 effective observations

Total carriers

6

0 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

G139R is present in 6 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 125% of WT with a standard error of 20%. 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 (%)
-0.768 0.003 2 0.425 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 – 6 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 G139R.
Neighbour residue Distance (Å) Observed variants
139 0 G139R, G139A, G139R,
138 4
140 4 S140Y,
137 5
141 5 P141fsX, P141S, P141L,
136 7
142 7 A142T,
135 8
143 8
134 8 E134X,
144 8 D144V,
133 9 M133T,
145 9
132 10 V132X,
146 10 N146X,
131 11 V131fsX, V131L, V131L,
147 11 H147R, H147X,
130 11 E130K,
148 11 R148fsX, R148Q, R148Y, R148W,
129 12 F129C,
149 12 G149V, G149A,
128 13 N128S,
150 13 P150L,
127 13
151 13 P151fsX, P151X,
126 14
152 14 T152S, T152S, T152I, T152X, T152fsX,
125 14
153 14 S153R, S153R, S153R,
124 15 M124T, M124R,
154 15 W154R, W154X, W154R,