KCNH2 Variant S153R

Summary of observed carriers, functional annotations, and structural context for KCNH2 S153R. 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

S153R 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: 93% 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 (%)
-0.803 0.04 -2 0.342 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 S153R.
Neighbour residue Distance (Å) Observed variants
153 0 S153R, S153R, S153R,
152 4 T152I, T152X, T152fsX, T152S, T152S,
154 4 W154R, W154R, W154X,
151 5 P151X, P151fsX,
155 5
150 7 P150L,
156 7
149 8 G149V, G149A,
157 8 P157X,
148 8 R148Q, R148fsX, R148W, R148Y,
158 8
147 9 H147R, H147X,
159 9
146 10 N146X,
160 10
145 11
161 11
144 11 D144V,
162 11 T162X,
143 12
163 12
142 13 A142T,
164 13 R164H, R164C,
141 13 P141fsX, P141L, P141S,
165 13
140 14 S140Y,
166 14
139 14 G139R, G139R, G139A,
167 14
138 15
168 15