C566A Summary

KCNH2 C566A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. C566A is not present in gnomAD. C566A has been functionally characterized in 2 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 5 individuals unaffected with LQT2 and 5 individuals affected with LQT2.


C566A 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.

C566A 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
19892739 2016 Xeno

C566A 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 -5.10 -2.20
19892739 2016 Xeno -9.40

C566A 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
-6 NA NA NA NA

C566A 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
420 14.9 Y420C
421 13.7 T421fsX T421M
422 10.6 A422T
423 9.5
424 11.3
425 9.9
426 6.1 P426H
427 7.6 Y427C Y427H Y427S
428 9.6 S428fsX S428L S428X
429 8.3 A429P A429V
430 6.2
431 6.6 F431L
432 11.3
522 14.2 G522E
523 13.3
525 14.4 K525N
526 12.3
529 12.6
557 14.7
558 11.6 A558E A558P A558V
559 10.4 L559F L559H
560 10.6 I560fsX I560M
561 8 A561P A561T A561V
562 5.7 H562P H562Q H562R
563 7 W563C W563G W563X
564 6.4 L564L
565 3.6
567 4.8 I567M I567T
568 8.2 W568C
569 6.5 Y569C Y569H Y569X
570 7.2
571 9.6 I571L I571V
572 11.2 G572C G572D G572R G572S
573 10.9
574 12.1 M574L M574V
585 11.9 W585C
586 13.4 L586M
606 14.9 S606Del S606F S606P
607 11.7
608 13.7
609 12.6 D609G D609N
610 10.3
611 7.1 Y611D
612 10.9 V612A V612L
613 11 T613A T613K T613L T613M
614 7.6 A614T A614V
615 8.5 L615F L615V
616 13.8 Y616S
617 11.3 F617L F617V
618 9.5 T618S
619 12.4
620 15 S620G S620I
621 14.5 S621N S621R
622 14.2 L622F
636 14.8
637 13.8 E637G E637K E637X
640 10.7 F640Del F640L F640V
641 14.7 S641F S641P
642 15 I642Del I642V
643 14.3
644 13.1 V644F V644I