G187S Summary

KCNH2 G187S was found in 1 paper (see below) with a total of 1 carrier: 0 had LQT2. G187S is not present in gnomAD. G187S has been functionally characterized in 1 paper. Given the functional data available, we estimate this variant has "Normal" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Non_Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 9 individuals unaffected with LQT2 and 1 individuals affected with LQT2.

G187S Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
14661677 2003 1 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G187S Reported Functional Data: heterozygously collected

Steady state (S.S.) and peak tail current are relative % to wildtype (100% being no different from wildtype). V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype. Recovery from inactivation (Rec. inact.) and deactivation time (Deactivation) are the ratio of characteristic time constants with wildtype (unitless).

PMID Year Cell type S.S. peak current (%WT) Peak tail current (%WT) V0.5 act V0.5 inact Rec. inact. (%WT) Deactivation (%WT)
31493593 2019 HEK293 100 100

G187S Reported Functional Data: homozygously collected

PMID Year Cell type S.S. peak current (%WT) Peak tail current (%WT) V0.5 act V0.5 inact Rec. inact. (%WT) Deactivation (%WT)
31493593 2019 HEK293 100 0.00 0.00

G187S Predictions

PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 is considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. PAM scores reflect the chemistry difference between WT and variant amino acid (more negative being greater difference between the two). BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected.

PAM Score REVEL Score PROVEAN Score Polyphen2 Score BLAST-PSSM
-2 0.307 -0.481 0.002 1

G187S has 30 neighbors (found in individuals) within 15 ångströms

A residue within a folded protein on average has nearest neighbors that fall roughly into two shells: a "nearest" neighbor around 5-6 angstroms and a second shell around 11 angstroms. NOTE: some residues appear multiple times at different distances. This results from the fact that the functional Kv11.1 channel is a homotetramer and occasionally the same residue from multiple subunits is present within the 15A window. All variants shown in the rightmost column have been observed in at least one individual in the literature or gnomAD.

ResidueNumber Distance(Å) Variants
172 14.7 A172V
173 14.2
174 13.7
175 13.2 A175D A175S A175X
176 12.6 R176Q R176W R176X
177 12 E177X
178 11.4
179 10.7 S179W
180 10.1
181 9.3 R181fsX R181Q R181W
182 8.5 S182X
183 7.6 G183fsX
184 6.6 G184Del
185 5.4
186 3.8 G186fsX
188 3.8 A188P A188S A188X
189 5.4 G189Ins
190 6.6 A190T A190V
191 7.6 P191fsX P191Q
192 8.5 G192fsX
193 9.3 A193fsX A193T A193V A193X
194 10.1 V194M
195 10.7
196 11.4
197 12 D197N D197Y
198 12.6 V198L
199 13.2
200 13.7 L200Q
201 14.2
202 14.7