KCNH2 Variant T152S

Summary of observed carriers, functional annotations, and structural context for KCNH2 T152S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

7%

0/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

T152S is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 94% of WT with a standard error of 23%. 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 (%)
-0.463 0.0 1 0.367 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 – 1 1 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 T152S.
Neighbour residue Distance (Å) Observed variants
152 0 T152I, T152X, T152fsX, T152S, T152S,
151 4 P151X, P151fsX,
153 4 S153R, S153R, S153R,
150 5 P150L,
154 5 W154R, W154R, W154X,
149 7 G149V, G149A,
155 7
148 8 R148Q, R148fsX, R148W, R148Y,
156 8
147 8 H147R, H147X,
157 8 P157X,
146 9 N146X,
158 9
145 10
159 10
144 11 D144V,
160 11
143 11
161 11
142 12 A142T,
162 12 T162X,
141 13 P141fsX, P141L, P141S,
163 13
140 13 S140Y,
164 13 R164H, R164C,
139 14 G139R, G139R, G139A,
165 14
138 14
166 14
137 15
167 15