A661C Summary

KCNH2 A661C was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. A661C is not present in gnomAD. A661C has been functionally characterized in 2 papers. 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 9 individuals unaffected with LQT2 and 1 individuals affected with LQT2.


A661C 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.

A661C 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)
18955593 2008 Xeno
19892759 2036 Xeno

A661C 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)
18955593 2008 Xeno 21.7 151.8
19892759 2036 Xeno -4.10

A661C 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

A661C has 53 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
543 13.9 S543fsX
546 10.6
547 12 A547T
548 13.5
549 10.5 V549M
550 10.1
552 14.6 L552S
553 11 L553V
554 13.5
649 14.5
650 12.1 L650X
651 14.5 M651K
652 14.1 Y652X
653 10.1
653 12.1
654 11
654 9.5
655 10.6
655 13.5
656 14.7 F656L
656 10 F656L
657 10 G657S G657V
657 14.4 G657S G657V
657 6 G657S G657V
658 5.7
658 10.6
659 14.9
659 5.6
660 4.1 S660L
660 11.5 S660L
660 13.5 S660L
662 4
663 12.9
663 5.5
664 4.7 Q664X
664 9.6 Q664X
665 6.1 R665Q
666 8.7
667 10.2 Y667X
667 14.5 Y667X
668 13.9 S668L
668 9.8 S668L
669 13.2 G669C G669R G669X
669 15 G669C G669R G669X
670 13.4
670 13.4
671 10.4 A671Del A671G
671 11.9 A671Del A671G
672 14.5 R672C R672H
672 13.9 R672C R672H
674 11.7 H674fsX H674Y
675 11.2
678 13.3