F125C Summary

KCNH2 F125C was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. F125C is not present in gnomAD. F125C 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 5 individuals unaffected with LQT2 and 5 individuals affected with LQT2.


F125C Reported Clinical Data

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

F125C 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)
25417810 2014 HEK293

F125C 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)
25417810 2014 HEK293 55 -2.90 73.7

F125C 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
-13 0.976 -5.157 0.977 4

F125C has 62 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
12 14.9 N12D
14 12.8
15 12 L15V
18 12.5 I18M
19 14.5 I19F
22 14.3 F22S F22Y
29 11.7 F29L F29S F29V
30 8.7 I30Del I30T
31 7.3 I31S
32 4.7 A32T
33 7 N33T
34 6.8 A34T
35 10.3 R35W
36 10.4 V36X
37 13.9
38 11.9
39 7.2 C39R C39X
40 9.3
41 9.8 V41A
42 10.2 I42N
43 12.8 Y43C Y43D
44 14.5 C44F C44W C44X
60 14.6 M60T
63 11.5 P63H
64 7.2 C64R C64Y
65 10.6 T65P
66 12.5 C66G C66R C66Y
82 10.7 I82Del I82dup I82Ins I82T
83 10.7 A83fsX A83P
84 13.2
85 8.5 A85P A85V
86 6 L86R
87 9.7 L87P
88 10.3
89 9 A89G A89V
90 9.7 E90K
91 11.9
92 11.6 R92C R92L
93 14.7 K93R K93X
94 14.1 V94A V94L
110 12 V110A
111 10.8 D111V
112 7.3 V112M
113 7.3 V113Del
114 5.8 P114S
115 7.3 V115M
116 10 K116Q
117 13.1
120 13.8
121 10.7 A121fsX
122 6.9
123 7.4
124 5.2 M124R M124T
126 6.1
127 7.1
128 11.8 N128S
129 13 F129C
794 14.1 V794D V794I
795 12 V795I
796 13.2 V796Del V796L
797 14.5 A797T
798 14 I798fsX