I639L Summary

KCNH2 I639L was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I639L is not present in gnomAD. I639L 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.


I639L 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.

I639L 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 0.754 -1.8 0.226 1

I639L has 53 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
558 13.4 A558E A558P A558V
561 13.7 A561P A561T A561V
562 13.7 H562P H562Q H562R
564 12.7 L564L
565 14
567 11.9 I567M I567T
568 10.8 W568C
570 13.3
571 9.9 I571L I571V
572 13.6 G572C G572D G572R G572S
575 12.4 E575K
584 14.3 G584C G584R G584S
585 14 W585C
593 15 I593K I593R I593T I593V I593X
606 14.2 S606Del S606F S606P
607 14.5
608 9.6
609 10.2 D609G D609N
610 14
611 10 Y611D
612 6.7 V612A V612L
613 9.8 T613A T613K T613L T613M
614 11.2 A614T A614V
615 8.7 L615F L615V
616 8.4 Y616S
617 13.1 F617L F617V
617 13.6 F617L F617V
618 14.1 T618S
618 13.2 T618S
619 10.6
620 12.9 S620G S620I
621 12.9 S621N S621R
623 14.9 T623I
627 12.8 F627fsX F627L F627X
629 13.7 N629D N629I N629K N629S N629T
630 14.5 V630A V630I V630T
631 12.9 S631F
632 9.3 P632A P632S
633 11.4 N633D N633I N633S
634 8.5 T634A T634I T634P T634S
635 6.6 N635I
636 5.3
637 7.4 E637G E637K E637X
638 5.7 K638D K638Del K638E K638R
640 6.2 F640Del F640L F640V
641 6.4 S641F S641P
642 5.4 I642Del I642V
643 6.9
644 9.5 V644F V644I
645 9.9 M645I M645L M645R M645V
646 11
647 12.7
648 14.7 G648A