H254Q Summary

KCNH2 H254Q was found in 1 paper (see below) with a total of 1 carrier: 0 had LQT2. H254Q is not present in gnomAD. H254Q 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.

H254Q 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.

H254Q 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)
31493596 2019 HEK293 100 100

H254Q 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)
31493596 2019 HEK293 100 0.00 0.00

H254Q 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
1 0.49 -0.996 0.001 2

H254Q 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
239 14.7 S239P S239X
240 14.2 P240L
241 13.7 P241fsX P241L P241S
242 13.2 R242C R242X
243 12.6 S243R S243X
244 12 A244E A244G
245 11.4 P245R
246 10.7
247 10.1 Q247R Q247X
248 9.3
249 8.5
250 7.6
251 6.6 P251A
252 5.4 R252fsX R252Q
253 3.8
255 3.8
256 5.4
257 6.6 N257H
258 7.6 P258L
259 8.5 D259N D259X
260 9.3 A260V
261 10.1 S261X
262 10.7 G262fsX G262X
263 11.4
264 12
265 12.6
266 13.2 S266G
267 13.7
268 14.2 A268X
269 14.7