KCNH2 Variant G149V

Summary of observed carriers, functional annotations, and structural context for KCNH2 G149V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

5%

0/15 effective observations

Total carriers

5

0 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

G149V is present in 5 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 124% of WT with a standard error of 14%. 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 (%)
0.024 0.0 1 0.365 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 – 5 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 G149V.
Neighbour residue Distance (Å) Observed variants
149 0 G149V, G149A,
148 4 R148fsX, R148Q, R148Y, R148W,
150 4 P150L,
147 5 H147R, H147X,
151 5 P151fsX, P151X,
146 7 N146X,
152 7 T152S, T152S, T152I, T152X, T152fsX,
145 8
153 8 S153R, S153R, S153R,
144 8 D144V,
154 8 W154R, W154X, W154R,
143 9
155 9
142 10 A142T,
156 10
141 11 P141fsX, P141S, P141L
157 11 P157X,
140 11 S140Y,
158 11
139 12 G139R, G139A, G139R,
159 12
138 13
160 13
137 13
161 13
136 14
162 14 T162X,
135 14
163 14
134 15 E134X,
164 15 R164C, R164H,