I593V Summary

KCNH2 I593V was found in 1 paper (see below) with a total of 3 carriers: 2 had LQT2. I593V is not present in gnomAD. I593V 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 6 individuals unaffected with LQT2 and 4 individuals affected with LQT2.


I593V Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
Japan Cohort 2020 2 1 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

I593V 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
2 0.717 -0.814 0.236 2

I593V has 45 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
575 14 E575K
577 13
583 7.6 I583V
584 9.4 G584C G584R G584S
584 13.9 G584C G584R G584S
585 14.6 W585C
585 11.9 W585C
586 10.4 L586M
587 11.5
587 13.2
588 12.8 N588D N588K
588 9.1 N588D N588K
589 5.3 L589P
590 5.2 G590D G590V
591 7 D591H D591N
592 4.9 Q592X
594 4.3
595 5.1 K595E K595N
596 8.5 P596L P596R P596S P596T
597 11.2 Y597C Y597H
603 12.5 G603D
604 9.3 G604C G604D G604S
605 7.6 P605L
606 9 S606Del S606F S606P
607 12.7
608 12.3
609 8.6 D609G D609N
610 10.4
612 11.8 V612A V612L
613 10 T613A T613K T613L T613M
614 13.7 A614T A614V
616 13.1 Y616S
628 13.9 G628A G628D G628Del G628R G628S G628V
629 10.5 N629D N629I N629K N629S N629T
630 11.9 V630A V630I V630T
631 12.4 S631F
631 14.5 S631F
632 11.1 P632A P632S
633 6.9 N633D N633I N633S
634 8 T634A T634I T634P T634S
635 9.1 N635I
636 12.4
637 11.5 E637G E637K E637X
638 10.6 K638D K638Del K638E K638R
639 15 I639F I639N