I583V Summary

KCNH2 I583V was found in 1 paper (see below) with a total of 9 carriers: 1 had LQT2. I583V is not present in gnomAD. I583V 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 7 individuals unaffected with LQT2 and 3 individuals affected with LQT2.


I583V Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
Italy Cohort 2020 9 8 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

I583V 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 0.725 -0.823 0.236 3

I583V has 42 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
568 13.6 W568C
570 14.9
571 12.3 I571L I571V
572 10 G572C G572D G572R G572S
573 12.6
574 14.8 M574L M574V
575 9.8 E575K
576 8.7
577 7.6
584 3.9 G584C G584R G584S
585 9.6 W585C
586 9.1 L586M
587 5.9
588 8.2 N588D N588K
588 14.8 N588D N588K
589 11.9 L589P
589 12.3 L589P
590 12 G590D G590V
590 11.6 G590D G590V
591 11.1 D591H D591N
591 12 D591H D591N
592 9.1 Q592X
592 13.9 Q592X
593 7.6 I593K I593R I593T I593V I593X
594 8.5
595 10.9 K595E K595N
596 14.1 P596L P596R P596S P596T
596 13.9 P596L P596R P596S P596T
597 11.4 Y597C Y597H
605 14.6 P605L
606 14.7 S606Del S606F S606P
609 14 D609G D609N
629 12.8 N629D N629I N629K N629S N629T
630 13.6 V630A V630I V630T
631 11.4 S631F
632 11.1 P632A P632S
633 7.3 N633D N633I N633S
634 7.5 T634A T634I T634P T634S
635 11.1 N635I
636 11.6
637 9.8 E637G E637K E637X
638 12.5 K638D K638Del K638E K638R