D837A Summary

KCNH2 D837A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. D837A is not present in gnomAD. D837A 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.


D837A 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.

D837A 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 0.96 -7.179 0.988 -2

D837A has 36 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
729 14
733 14.7
750 13.8 C750X
751 14.8 L751V
753 9.8 A753S
754 9
755 10.5
756 10 M756V
757 4.6
758 8.7
759 9.3 K759N
760 14.3
776 13.7 L776I L776P
777 9.4
778 9.7 A778T
779 10.4
780 12.9
781 13.8
809 11.7
815 14.4
831 14
832 9.6
833 6.4
834 4.9 H834R
835 7.8 R835fsX R835Q R835W
836 4.9
838 5.5 L838R
839 7.2
840 5.9 E840Q
841 7.9 V841L
842 10.4
843 11.3
844 12.3 M844V
845 13.5
852 14.2
853 14.5 W853X