H562Q Summary

KCNH2 H562Q was found in 1 paper (see below) with a total of 2 carriers: 0 had LQT2. H562Q is not present in gnomAD. H562Q has been functionally characterized in 1 paper. 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.


H562Q Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
Japan Cohort 2020 2 2 0
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

H562Q 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)
22517356 2012 Xeno

H562Q 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)
22517356 2012 Xeno 8 -11.20

H562Q 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
1 0.92 -7.668 0.989 0

H562Q has 61 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
418 13.5
419 10.6
420 11.9 Y420C
421 11.1 T421fsX T421M
422 7.4 A422T
423 5.7
424 9
425 9.6
426 6.8 P426H
427 8.1 Y427C Y427H Y427S
428 11 S428fsX S428L S428X
429 11.5 A429P A429V
430 10.6
431 10 F431L
432 14.5
526 13.9
528 14.9 R528P R528W R528X
529 11.8
532 13.8
554 13.7
555 10.9
556 10.4
557 10.4
558 6.4 A558E A558P A558V
559 5.5 L559F L559H
560 7.5 I560fsX I560M
561 5.1 A561P A561T A561V
563 5.2 W563C W563G W563X
564 7.2 L564L
565 5.7
566 5.7 C566F C566G C566R C566S
567 9.2 I567M I567T
568 11.9 W568C
569 11.5 Y569C Y569H Y569X
570 12.8
571 14.8 I571L I571V
607 13.7
608 13.4
609 13.7 D609G D609N
610 13.3
611 6.8 Y611D
612 10.4 V612A V612L
613 12.2 T613A T613K T613L T613M
614 9 A614T A614V
615 6.8 L615F L615V
616 13.2 Y616S
617 12.3 F617L F617V
618 9 T618S
619 9.6
620 14.1 S620G S620I
621 14.2 S621N S621R
622 12.4 L622F
638 14.9 K638D K638Del K638E K638R
639 13.7 I639F I639N
640 13.6 F640Del F640L F640V
642 11.9 I642Del I642V
644 13.6 V644F V644I
645 14.6 M645I M645L M645R M645V
646 13.6
647 14.8
651 14.9 M651K