I642M Summary

KCNH2 I642M was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I642M is not present in gnomAD. I642M 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 3 individuals unaffected with LQT2 and 7 individuals affected with LQT2.


I642M 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.

I642M 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
NA 0.818 -2.9 0.998 1

I642M has 68 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
554 12.5
555 14.4
556 14.9
557 10.6
558 9.9 A558E A558P A558V
559 13.4 L559F L559H
560 13.3 I560fsX I560M
561 10 A561P A561T A561V
562 11.9 H562P H562Q H562R
564 12.4 L564L
564 13.6 L564L
565 12.1
566 15 C566F C566G C566R C566S
567 13.7 I567M I567T
568 15 W568C
568 12.3 W568C
571 13.6 I571L I571V
608 13.4
609 12.9 D609G D609N
611 10.6 Y611D
612 8.3 V612A V612L
613 10 T613A T613K T613L T613M
614 10 A614T A614V
615 6.5 L615F L615V
616 6.5 Y616S
617 10.6 F617L F617V
617 12 F617L F617V
618 12.5 T618S
618 9.3 T618S
619 5.6
620 13.3 S620G S620I
620 8.5 S620G S620I
621 9.6 S621N S621R
621 11.7 S621N S621R
622 11.8 L622F
622 10.9 L622F
623 14.7 T623I
623 9.6 T623I
624 12.9 S624N S624R
624 13.2 S624N S624R
625 10.8 V625E
626 12.2 G626A G626S G626V
626 14 G626A G626S G626V
627 10.1 F627fsX F627L F627X
628 14.4 G628A G628D G628Del G628R G628S G628V
629 13.1 N629D N629I N629K N629S N629T
630 13 V630A V630I V630T
631 12.9 S631F
632 9.9 P632A P632S
633 13.3 N633D N633I N633S
634 12.1 T634A T634I T634P T634S
635 10.9 N635I
636 10.1
637 10.3 E637G E637K E637X
638 7.3 K638D K638Del K638E K638R
639 5.4 I639F I639N
640 7.1 F640Del F640L F640V
641 4.2 S641F S641P
643 5.1
644 6.5 V644F V644I
645 4.9 M645I M645L M645R M645V
646 6.5
647 9.4
648 10.4 G648A
649 10.7
650 13.2 L650X
651 14.9 M651K
652 14.5 Y652X