I96V Summary

KCNH2 I96V was found in 1 paper (see below) with a total of 2 carriers: 1 had LQT2. I96V is not present in gnomAD. I96V 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 Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 6 individuals unaffected with LQT2 and 4 individuals affected with LQT2.


I96V Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
Japan Cohort 2020 2 1 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

I96V 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)
31493592 2019 HEK293 100 100

I96V 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)
31493592 2019 HEK293 100 -1.60 -2.00

I96V 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
2 0.431 -0.422 0.004 2

I96V has 48 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
28 14.1 K28E
48 14.3
51 12.8
52 13.9 C52W
64 13.7 C64R C64Y
65 11.2 T65P
66 10.7 C66G C66R C66Y
67 12.4
68 13 F68L F68V
69 9.1 L69Del L69P
70 7.9 H70Q H70R
71 9.4 G71E G71R G71W
72 11.3 P72Q P72R P72S P72T
73 8.3 R73C R73fsX R73G R73H
74 6.6 T74fsX T74M
75 7 Q75X
76 10.1
77 9.7 R77S
78 6.3 A78P A78T
79 7.4 A79Del A79fsX A79S A79T
80 10.5 A80P
81 9.2 Q81E Q81H Q81P Q81X
82 8.6 I82Del I82dup I82Ins I82T
83 12.6 A83fsX A83P
84 14.4
85 13.9 A85P A85V
92 13.4 R92C R92L
93 11.5 K93R K93X
94 6.6 V94A V94L
95 5.2 E95G E95K
97 4
98 5
99 9.5 Y99N Y99S
100 12.6 R100G R100P R100Q
104 13.8
105 10
106 8.3 F106L F106V
107 6.9 L107P
108 6 C108Y
109 7.9 L109P L109Q L109X
110 7 V110A
111 12.2 D111V
112 12.6 V112M
127 12.4
128 13.1 N128S
129 10 F129C
130 12.2 E130K
131 11.1 V131fsX V131L