A453D Summary

KCNH2 A453D was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. A453D is not present in gnomAD. A453D 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 3 individuals unaffected with LQT2 and 7 individuals affected with LQT2.

A453D 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.

A453D 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 0.52 0.374 0.001 0

A453D has 29 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
417 14.5
420 10.4 Y420C
421 13.2 T421fsX T421M
423 14.5
424 10.4
425 12.2
426 14.8 P426H
427 13.1 Y427C Y427H Y427S
428 10.7 S428fsX S428L S428X
429 14.1 A429P A429V
432 13.2
449 8
450 5.6
451 6 P451L
452 4.4
454 3.9
455 5.7
456 5.3 D456Y
457 6.4 L457P
458 8.8
459 10.1
460 10.1 D460fsX
461 12.6
462 14.9 M462Ins
507 13.6 P507L P507S
509 14.1 D509N
522 14.8 G522E
525 11.7 K525N
528 12.2 R528P R528W R528X