K595E Summary

KCNH2 K595E was found in 1 paper (see below) with a total of 4 carriers: 2 had LQT2. K595E is not present in gnomAD. K595E has been functionally characterized in 1 paper. This residue is located in a Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 3 individuals unaffected with LQT2 and 7 individuals affected with LQT2.

K595E Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
Japan Cohort 2020 1 1 0
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

K595E 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)
19419905 2009 CHO 10.7 108.5

K595E 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)
19419905 2009 CHO

K595E 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
-4 0.801 -3.427 0.236 1

K595E has 29 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
577 14.2
583 10.9 I583V
584 13.7 G584C G584R G584S
585 13.6 W585C
586 10.6 L586M
587 11.1
588 11.5 N588D N588K
589 7.7 L589P
590 5.6 G590D G590V
591 8.5 D591H D591N
592 9.3 Q592X
593 5.1 I593K I593R I593T I593V I593X
594 3.2
596 5.3 P596L P596R P596S P596T
597 8.1 Y597C Y597H
603 7.9 G603D
604 5 G604C G604D G604S
605 5.1 P605L
606 7.4 S606Del S606F S606P
607 11.4
608 12.6
609 9.7 D609G D609N
610 10.2
612 14.2 V612A V612L
613 12.9 T613A T613K T613L T613M
633 11.9 N633D N633I N633S
634 12 T634A T634I T634P T634S
635 11.7 N635I
638 14.6 K638D K638Del K638E K638R