E50D Summary

KCNH2 E50D was found in 1 paper (see below) with a total of 0 carriers: 0 had LQT2. E50D is not present in gnomAD. E50D 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 4 individuals unaffected with LQT2 and 6 individuals affected with LQT2.

E50D Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
29759541 2017 2 0 Short QT
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E50D 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)

E50D 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)

E50D 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 0.621 -1.366 0 0

E50D 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
23 14.1
26 11.2 S26I
27 10.7 R27P R27X
28 8.5 K28E
29 12.1 F29L F29S F29V
30 13.8 I30Del I30T
43 13.8 Y43C Y43D
44 11.1 C44F C44W C44X
45 8.3 N45D N45K
46 6.4 D46E D46Y
47 4.3 G47C G47V
48 7.5
49 5.2 C49G C49R
51 5.9
52 7.4 C52W
53 7.2 G53R G53S
54 10.9 Y54N Y54X
55 10.7 S55L
56 11.7 R56Q
58 14.3 E58D E58K
59 13.5
69 14.5 L69Del L69P
98 14.7
100 10.1 R100G R100P R100Q
101 11.9 K101E
102 12.8 D102H D102V D102X
104 13.3
106 12.1 F106L F106V
108 14.2 C108Y
128 14.3 N128S
129 12 F129C
130 12.8 E130K
131 13.1 V131fsX V131L
741 14.4 K741R
802 14.6