G657I Summary

KCNH2 G657I was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. G657I is not present in gnomAD. G657I 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.


G657I 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.

G657I 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)
17823114 2007 Xeno

G657I 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)
17823114 2007 Xeno -53.70 71.8

G657I 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
-11 NA NA NA NA

G657I has 57 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 14.4
549 12.1 V549M
550 11.1
552 14.1 L552S
553 9.4 L553V
554 11.7
556 13.8
557 12.5
622 15 L622F
623 14.5 T623I
648 13 G648A
648 14.1 G648A
649 11.3
649 12.6
650 11.2 L650X
650 10.8 L650X
651 10 M651K
651 13.8 M651K
652 8.7 Y652X
652 12.4 Y652X
652 13.3 Y652X
653 14.5
653 13.5
653 8.1
653 6.1
654 5.6
654 9.9
655 13.6
655 6.1
656 13.6 F656L
656 11.7 F656L
656 5.7 F656L
658 3.7
658 13.1
658 12.5
659 5.2
659 10.8
660 13.5 S660L
660 4.7 S660L
660 14.5 S660L
660 7.1 S660L
661 6 A661V
661 10 A661V
661 14.4 A661V
662 8.2
662 12.8
663 9.6
663 9.5
664 9.8 Q664X
664 8.4 Q664X
665 11.5 R665Q
666 14
666 14.9
667 13.1 Y667X
668 14.6 S668L
670 14.6
671 12.7 A671Del A671G