A653C Summary

KCNH2 A653C was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. A653C is not present in gnomAD. A653C 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.


A653C 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.

A653C 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)
19406877 2009 CHO

A653C 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)
19406877 2009 CHO -26.60 400

A653C 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

A653C has 60 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
550 12.5
553 13.1 L553V
553 11.7 L553V
554 13.2
554 11.6
556 13.7
557 12.9
557 11.2
560 13.6 I560fsX I560M
621 14.2 S621N S621R
622 14.5 L622F
622 10.8 L622F
623 11.2 T623I
623 11.7 T623I
624 13.1 S624N S624R
624 11.8 S624N S624R
624 14.3 S624N S624R
644 13.6 V644F V644I
645 13.3 M645I M645L M645R M645V
646 11.5
647 10.2
648 14.2 G648A
648 7.6 G648A
648 14.8 G648A
649 11.1
649 14.8
649 6.5
650 5.9 L650X
650 13 L650X
651 6.3 M651K
651 13.7 M651K
652 8.3 Y652X
652 5.3 Y652X
652 13.8 Y652X
652 12.3 Y652X
654 13.5
654 3.9
654 12.1
655 6.3
655 10.6
656 6.6 F656L
656 6.5 F656L
657 13.5 G657S G657V
657 6.1 G657S G657V
657 14.5 G657S G657V
657 8.1 G657S G657V
658 8.3
658 10.9
659 7.6
659 10.1
660 13.6 S660L
660 10.2 S660L
660 6.1 S660L
661 12.1 A661V
661 10.1 A661V
662 11.7
662 14
663 9.3
664 10.9 Q664X
667 14.3 Y667X