I684M Summary

KCNH2 I684M was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I684M is not present in gnomAD. I684M has been functionally characterized in 0 papers. This residue is located in a Mild_Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 9 individuals unaffected with LQT2 and 1 individuals affected with LQT2.


I684M 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.

I684M 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 0.85 -2.913 0.973 1

I684M has 50 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
5 14.7
544 13.8 E544A E544fsX
545 14.8
675 14.8
676 13.1 Q676fsX Q676X
677 10 M677T
678 10.2
679 11.2 R679Q R679W
680 5.9
681 6.9 R681W
682 7.4 E682X
683 4.9
685 5.6 R685C R685H R685P
686 7.7
687 6.6
688 7.1
689 4.8
690 8.4
691 10.4
692 12
693 9 L693X
694 6 R694C R694H
695 11.7
696 12.8 R696C R696H
697 8.1 L697X
698 8.9 E698K E698X
699 13.8 E699D
700 14.6
701 12.3
702 14.4
707 13.4
708 12.7
709 12
710 14.2
711 11.3 I711V
712 14.2 D712N
713 11 M713V
715 14.2 A715A A715sp A715T A715V
716 10.7 V716G
717 12.3 L717P
719 14.9
720 12.2
724 13.3 C723X L724X
725 14.7 Q725fsX Q725R
727 12.8
728 10
729 13.6
731 10.2 H731R
732 11.4
734 14.1 R734C R734H