E637G Summary

KCNH2 E637G was found in 2 papers (see below) with a total of 4 carriers: 4 had LQT2. E637G is not present in gnomAD. E637G has been functionally characterized in 1 paper. Given the functional data available, we estimate this variant has "Severe Dominant LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). 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 1 individuals unaffected with LQT2 and 9 individuals affected with LQT2.


E637G Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
21109023 2011 3 0 3
21216356 2011 1 0 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E637G 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)
21109023 2011 CHO 100 8.8 -31.5 107.7

E637G 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)
21109023 2011 CHO 50 0 10.00 59.40 72.4

E637G 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
-4 0.865 -6.767 0.999 -2

E637G has 64 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
564 12.3 L564L
565 12.1
566 13.8 C566F C566G C566R C566S
567 10.8 I567M I567T
568 6.1 W568C
569 11.5 Y569C Y569H Y569X
570 9.9
571 6.2 I571L I571V
572 7.9 G572C G572D G572R G572S
573 11.5
574 12.3 M574L M574V
575 8.9 E575K
576 12.4
577 13.3
583 9.8 I583V
584 7.2 G584C G584R G584S
585 6.9 W585C
586 10.1 L586M
587 11.9
588 11.1 N588D N588K
589 13.6 L589P
589 13.2 L589P
592 11.9 Q592X
593 11.5 I593K I593R I593T I593V I593X
608 13
609 11.7 D609G D609N
610 14.6
612 10.5 V612A V612L
613 11.1 T613A T613K T613L T613M
613 12.9 T613A T613K T613L T613M
614 14.2 A614T A614V
614 11.6 A614T A614V
615 13.6 L615F L615V
616 9.3 Y616S
616 14.6 Y616S
617 9.4 F617L F617V
618 12.2 T618S
619 15
620 14.4 S620G S620I
620 14.1 S620G S620I
621 12.3 S621N S621R
626 14.9 G626A G626S G626V
626 14.8 G626A G626S G626V
627 10.9 F627fsX F627L F627X
628 13.2 G628A G628D G628Del G628R G628S G628V
628 13.2 G628A G628D G628Del G628R G628S G628V
629 14.3 N629D N629I N629K N629S N629T
629 10.2 N629D N629I N629K N629S N629T
630 9.8 V630A V630I V630T
630 13.3 V630A V630I V630T
631 7.5 S631F
632 4.8 P632A P632S
633 6 N633D N633I N633S
634 3.9 T634A T634I T634P T634S
635 6.8 N635I
636 4.3
638 5.4 K638D K638Del K638E K638R
639 7.4 I639F I639N
640 6.9 F640Del F640L F640V
641 7.7 S641F S641P
642 10.3 I642Del I642V
643 11.5
644 11.5 V644F V644I
645 12.6 M645I M645L M645R M645V