G594D Summary

KCNH2 G594D was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. G594D is not present in gnomAD. G594D 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 4 individuals unaffected with LQT2 and 6 individuals affected with LQT2.

G594D 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.

G594D 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 0.875 -5.6 0.971 -2

G594D has 31 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
577 12.4
583 8.5 I583V
584 11.6 G584C G584R G584S
585 14.9 W585C
586 12.3 L586M
587 13.9
587 12.2
588 14.8 N588D N588K
588 11.4 N588D N588K
589 8.4 L589P
590 5.8 G590D G590V
591 7.4 D591H D591N
592 8.1 Q592X
593 4.3 I593K I593R I593T I593V I593X
595 3.2 K595E K595N
596 5.9 P596L P596R P596S P596T
597 10 Y597C Y597H
603 10.6 G603D
604 8.1 G604C G604D G604S
605 8.1 P605L
606 10 S606Del S606F S606P
607 14.2
608 14.5
609 11.5 D609G D609N
610 12.7
613 14 T613A T613K T613L T613M
629 14.5 N629D N629I N629K N629S N629T
633 10.7 N633D N633I N633S
634 11.4 T634A T634I T634P T634S
635 12.3 N635I
638 14.7 K638D K638Del K638E K638R