K638E Summary

KCNH2 K638E was found in 3 papers (see below) with a total of 4 carriers: 4 had LQT2. K638E is not present in gnomAD. K638E has been functionally characterized in 0 papers. 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 2 individuals unaffected with LQT2 and 8 individuals affected with LQT2.


K638E Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
10973849 2000 1 0 1
11854117 2002 3 0 3
22378279 1 0
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

K638E 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 0.879 -3.862 1 1

K638E has 71 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
561 14.2 A561P A561T A561V
562 14.9 H562P H562Q H562R
564 14.8 L564L
565 13
567 14.4 I567M I567T
568 10.5 W568C
568 13.8 W568C
570 14.8
571 11 I571L I571V
572 13.2 G572C G572D G572R G572S
575 12.8 E575K
583 12.5 I583V
584 10.8 G584C G584R G584S
585 12.9 W585C
585 11.7 W585C
586 14.2 L586M
588 13.9 N588D N588K
588 14.2 N588D N588K
589 10.6 L589P
590 14.1 G590D G590V
592 10.7 Q592X
593 10.6 I593K I593R I593T I593V I593X
594 14.7
595 14.6 K595E K595N
605 13.9 P605L
606 12.4 S606Del S606F S606P
607 13.6
608 10.2
609 8 D609G D609N
610 11.6
611 10.2 Y611D
612 5.6 V612A V612L
613 6 T613A T613K T613L T613M
614 8.8 A614T A614V
615 8.5 L615F L615V
616 4.7 Y616S
617 10.3 F617L F617V
617 11.6 F617L F617V
618 11.7 T618S
618 14.2 T618S
619 10.8
620 10.6 S620G S620I
620 14.7 S620G S620I
621 14 S621N S621R
621 12.1 S621N S621R
623 14.4 T623I
625 13 V625E
626 12.4 G626A G626S G626V
626 14.1 G626A G626S G626V
627 9.1 F627fsX F627L F627X
628 11.1 G628A G628D G628Del G628R G628S G628V
628 13.6 G628A G628D G628Del G628R G628S G628V
629 8.2 N629D N629I N629K N629S N629T
630 11.9 V630A V630I V630T
630 9.4 V630A V630I V630T
631 8.5 S631F
631 13.5 S631F
632 4.8 P632A P632S
633 6.5 N633D N633I N633S
634 5.6 T634A T634I T634P T634S
635 5.4 N635I
636 6.3
637 5.4 E637G E637K E637X
639 5.7 I639F I639N
640 8.4 F640Del F640L F640V
641 6.3 S641F S641P
642 7.3 I642Del I642V
643 10.7
644 11.2 V644F V644I
645 10.2 M645I M645L M645R M645V
646 13.7