I663A Summary

KCNH2 I663A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I663A is not present in gnomAD. I663A 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 8 individuals unaffected with LQT2 and 2 individuals affected with LQT2.


I663A 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.

I663A 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)
18690032 2007 Xeno
19892761 2038 Xeno

I663A 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)
18690032 2007 Xeno 4.80
19892761 2038 Xeno 7.10

I663A 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
-5 NA NA NA NA

I663A has 47 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
546 9.4
547 9.5 A547T
548 12.2
549 10.6 V549M
550 8.2
551 14 F551L
552 14.6 L552S
553 11.7 L553V
553 13.8 L553V
554 12.1
647 14.4
648 14.3 G648A
649 13.1
650 9.4 L650X
651 11.2 M651K
652 14.3 Y652X
653 9.3
654 14.6
654 6.7
655 10.6
655 12.6
656 13.3 F656L
656 10.8 F656L
657 9.5 G657S G657V
657 9.6 G657S G657V
658 9.6
658 8.8
659 13.7
659 6
660 5.4 S660L
660 13.9 S660L
661 12.9 A661V
661 5.5 A661V
662 14.7
662 4.9
664 5.1 Q664X
665 7.8 R665Q
666 5.9
667 5.9 Y667X
668 9.3 S668L
669 11.6 G669C G669R G669X
670 10.7
671 10.7 A671Del A671G
672 13.8 R672C R672H
674 14.6 H674fsX H674Y
675 14.2
678 14.3