I647M Summary

KCNH2 I647M was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I647M is not present in gnomAD. I647M 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 4 individuals unaffected with LQT2 and 6 individuals affected with LQT2.


I647M 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.

I647M 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 0.725 -2.85 0.994 1

I647M has 58 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
550 13.1
551 14.8 F551L
553 14.9 L553V
553 14.8 L553V
554 9.8
555 14.5
556 12.6
557 10.7
557 11.6
558 13.2 A558E A558P A558V
558 13.3 A558E A558P A558V
559 13.4 L559F L559H
560 8.4 I560fsX I560M
561 10.5 A561P A561T A561V
562 14.8 H562P H562Q H562R
563 12.1 W563C W563G W563X
564 9.1 L564L
565 13.6
567 12.7 I567M I567T
568 14.5 W568C
616 14.9 Y616S
617 13.3 F617L F617V
618 10.5 T618S
619 11.3
619 12.4
620 12.9 S620G S620I
620 13.9 S620G S620I
621 9.6 S621N S621R
622 7.5 L622F
622 14.2 L622F
623 11.1 T623I
623 11.5 T623I
624 14.1 S624N S624R
624 12.3 S624N S624R
625 13.4 V625E
639 12.7 I639F I639N
640 9.8 F640Del F640L F640V
641 9.9 S641F S641P
642 9.4 I642Del I642V
643 5.9
644 5.4 V644F V644I
645 7.8 M645I M645L M645R M645V
646 5
648 4.2 G648A
649 6.1
650 5.6 L650X
651 6 M651K
652 12.7 Y652X
652 10.4 Y652X
653 10.2
654 10.5
655 11.1
655 14.7
656 13 F656L
656 11.4 F656L
659 12.9
660 14.3 S660L
663 14.4