D46A Summary

KCNH2 D46A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. D46A is not present in gnomAD. D46A has been functionally characterized in 0 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 5 individuals unaffected with LQT2 and 5 individuals affected with LQT2.


D46A 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.

D46A 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
NA 0.84 -4.796 0.139 -3

D46A has 49 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
19 11.6 I19F
20 14.8 R20G R20L
22 12.9 F22S F22Y
23 10.3
24 12.9
25 14 Q25P
26 10.3 S26I
27 9.6 R27P R27X
28 9.6 K28E
29 9.6 F29L F29S F29V
30 11.9 I30Del I30T
31 13.8 I31S
41 14.8 V41A
42 14.7 I42N
43 9.1 Y43C Y43D
44 7.3 C44F C44W C44X
45 4.5 N45D N45K
47 4.8 G47C G47V
48 8
49 5.8 C49G C49R
50 6.4 E50X
51 10.5
52 10.8 C52W
53 10.5 G53R G53S
54 12.9 Y54N Y54X
55 10 S55L
56 7.6 R56Q
57 13.3 A57P
58 14.1 E58D E58K
59 12.3
60 13.1 M60T
128 14.2 N128S
129 13.3 F129C
739 13.3 H739fsX
740 13.6 C740G C740W
741 12.7 K741R
782 13.9 I782fsX I782N
783 14.2 S783P
785 13.6 G785D G785fsX G785S
786 14.6
798 12.9 I798fsX
799 12.6 L799sp
800 10.3
801 9.3 K801T
802 9.2
803 10.6 D803X D803Y
804 14.4
857 13.7 E857X
859 13.3 T859M T859R