I858V Summary

KCNH2 I858V was found in 0 papers (see below) with a total of 1 carrier: 0 had LQT2. I858V is present in 1 out of 251378 alleles in gnomAD (0.000398%). I858V 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.


I858V 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.

I858V 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 0.644 -0.729 0.376 2

I858V has 60 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
44 13.6 C44F C44W C44X
55 10.4 S55L
56 9.8 R56Q
57 7.1 A57P
58 10.8 E58D E58K
59 12.7
60 10.6 M60T
61 11.6 Q61R
62 14.7 R62Q
736 14.2
740 12.5 C740G C740W
741 11.5 K741R
742 11.6
743 13.5
776 12.3 L776I L776P
777 14.8
778 11.8 A778T
779 8.5
780 10.7
781 9.5
782 11.6 I782fsX I782N
787 14
789 13.1
796 14.9 V796Del V796L
797 13.2 A797T
798 14.5 I798fsX
799 10.8 L799sp
800 12.9
802 12.1
803 8.8 D803X D803Y
804 4.9
805 7.6 F805C F805S
806 6.2 G806R
807 8.1 E807X
808 6.9
809 10.7
810 11.8
811 12.1
812 13.1 Y812S
816 14.1 G816V
818 14.3 S818A S818L S818W
819 13.7 N819K
820 14.8 G820R
822 14.8 V822L V822M
831 14.8
832 14.9
833 13.4
835 14.2 R835fsX R835Q R835W
838 14.1 L838R
852 10.7
853 9.4 W853X
854 10.9
855 10.2 S855R
856 6.2
857 5.7 E857X
859 4.7 T859M T859R
860 7.1
861 6.4 N861H N861I
862 9 L862P
863 14.2 R863P R863X