H578A Summary

KCNH2 H578A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. H578A is not present in gnomAD. H578A has been functionally characterized in 1 paper. This residue is located in a Mild_Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 7 individuals unaffected with LQT2 and 3 individuals affected with LQT2.


H578A 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.

H578A 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)
15975984 2005 Xeno

H578A 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)
15975984 2005 Xeno 2.30 -5.00

H578A 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
-7 NA NA NA NA

H578A has 30 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
563 14.7 W563C W563G W563X
564 14.2 L564L
565 13.7
566 13.2 C566F C566G C566R C566S
567 12.6 I567M I567T
568 12 W568C
569 11.4 Y569C Y569H Y569X
570 10.7
571 10.1 I571L I571V
572 9.3 G572C G572D G572R G572S
573 8.5
574 7.6 M574L M574V
575 6.6 E575K
576 5.4
577 3.8
579 3.8 M579I M579T M579V
580 5.4 D580Y
581 6.6
582 7.6 R582C R582H R582L R582P
583 8.5 I583V
584 9.3 G584C G584R G584S
585 10.1 W585C
586 10.7 L586M
587 11.4
588 12 N588D N588K
589 12.6 L589P
590 13.2 G590D G590V
591 13.7 D591H D591N
592 14.2 Q592X
593 14.7 I593K I593R I593T I593V I593X