H70R Summary

KCNH2 H70R was found in 4 papers (see below) with a total of 3 carriers: 3 had LQT2. H70R is not present in gnomAD. H70R has been functionally characterized in 2 papers. 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 4 individuals unaffected with LQT2 and 6 individuals affected with LQT2.


H70R Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
10973849 2000 2 0 2
11854117 2002 1 0 1
15840476 2005 1 0 1
22885918 2012 1 0 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

H70R 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)
10187793 1999 Xeno
21536673 2011 Xeno

H70R 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)
10187793 1999 Xeno -1.60 9.50
21536673 2011 Xeno 33 50

H70R 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 0.822 -2.523 0.989 -1

H70R has 46 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
48 14
51 13.7
52 12.1 C52W
53 14.7 G53R G53S
54 12.2 Y54N Y54X
59 13.7
62 12.6 R62Q
63 11.2 P63H
64 11.5 C64R C64Y
65 7.9 T65P
66 6.5 C66G C66R C66Y
67 5.4
68 6.9 F68L F68V
69 4.8 L69Del L69P
71 4.9 G71E G71R G71W
72 8.3 P72Q P72R P72S P72T
73 8.6 R73C R73fsX R73G R73H
74 5.8 T74fsX T74M
75 9.1 Q75X
76 9.5
77 11.6 R77S
78 9.6 A78P A78T
79 7.7 A79Del A79fsX A79S A79T
80 11.2 A80P
81 12.9 Q81E Q81H Q81P Q81X
82 10.3 I82Del I82dup I82Ins I82T
83 12.4 A83fsX A83P
94 12.9 V94A V94L
95 13.1 E95G E95K
96 7.9 I96T I96V
97 7.7
98 6.1
99 7.4 Y99N Y99S
100 11.8 R100G R100P R100Q
101 13.2 K101E
102 14.7 D102H D102V D102X
103 12.5
104 13.1
105 11.1
106 10.8 F106L F106V
107 13 L107P
108 11.8 C108Y
109 14.7 L109P L109Q L109X
110 12.3 V110A
127 14.2
129 13.4 F129C