G487R Summary

KCNH2 G487R was found in 1 paper (see below) with a total of 3 carriers: 0 had LQT2. G487R is not present in gnomAD. G487R 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 Mild_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.

G487R Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
22764740 2012 3 3
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G487R 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)
22764740 2012 HEK293 120.7 -0.6

G487R 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)
22764740 2012 HEK293 99 2.20

G487R 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
-9 0.613 -2.816 0.44 -1

G487R has 23 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
398 13.4 W398L W398X
399 13.4
400 14.7 I400N
470 13.8 N470D
471 9.9 F471X
472 10.2 R472C R472X
473 12.1 T473P
474 12.1 T474I
475 10.8 Y475C Y475Del
477 13.8
480 14.2 E480V
482 13.8 V482A
483 9.6 V483I
484 8.3
485 6.9 H485X
486 4
488 4.7 R488C R488H
489 5.8 I489F I489I
490 6 A490P A490T
491 6.9 V491I
492 10.4 H492Y
493 11.8 Y493C Y493F Y493H Y493Ins
494 10.8 F494Del