G294V Summary

KCNH2 G294V was found in 2 papers (see below) with a total of 0 carriers: 0 had LQT2. G294V is not present in gnomAD. G294V 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.

G294V Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
15913580 2005 1 0
29752375 2018 1 0 SIDS
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G294V 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)
29752375 2018 HEK293 100

G294V 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)
29752375 2018 HEK293 83 -3.50 106.7

G294V 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
-5 0.644 -1.772 0.149 -2

G294V 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
279 14.7
280 14.2
281 13.7 R281fsX R281X
282 13.2 A282X
283 12.6
284 12 S284X
285 11.4 A285fsX A285V
286 10.7 D286X
287 10.1 D287fsX
288 9.3
289 8.5 E289K
290 7.6
291 6.6
292 5.4
293 3.8
295 3.8 V295fsX
296 5.4 L296fsX
297 6.6 P297S
298 7.6 P298X
299 8.5
300 9.3
301 10.1
302 10.7 H302fsX H302H H302X
303 11.4
304 12 S304R
305 12.6
306 13.2 G306W
307 13.7 A307P
308 14.2 M308I M308R M308T M308V
309 14.7 H309Q H309Y