E90K Summary

KCNH2 E90K was found in 1 paper (see below) with a total of 3 carriers: 0 had LQT2. E90K is present in 3 out of 229564 alleles in gnomAD (0.001307%). E90K 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.

E90K Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
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.

E90K 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

E90K 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 111 4.00 100

E90K 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 0.698 -2.382 0.409 1

E90K has 35 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
32 14.3 A32T
34 14.2 A34T
64 14.3 C64R C64Y
80 13.9 A80P
81 11.6 Q81E Q81H Q81P Q81X
82 10.9 I82Del I82dup I82Ins I82T
83 11.2 A83fsX A83P
84 10.2
85 6 A85P A85V
86 8.4 L86R
87 9.5 L87P
88 5.7
89 3.7 A89G A89V
91 5.2
92 4.7 R92C R92L
93 10 K93R K93X
94 11.2 V94A V94L
109 14.6 L109P L109Q L109X
110 11.8 V110A
111 9.7 D111V
112 6.5 V112M
113 7.1 V113Del
114 5.8 P114S
115 10.1 V115M
116 9.7 K116Q
117 14.7
120 13.3
121 12.2 A121fsX
122 9.9
123 13.3
124 13.1 M124R M124T
125 9.7
126 11
127 11.9
128 13.8 N128S