H485Q Summary

KCNH2 H485Q was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. H485Q is not present in gnomAD. H485Q has been functionally characterized in 1 paper. 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 8 individuals unaffected with LQT2 and 2 individuals affected with LQT2.

H485Q 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.

H485Q Reported Functional Data: heterozygously collected

Steady state (S.S.) and peak tail current are relative % to wildtype (100% being no different from wildtype). V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype. Recovery from inactivation (Rec. inact.) and deactivation time (Deactivation) are the ratio of characteristic time constants with wildtype (unitless).

PMID Year Cell type S.S. peak current (%WT) Peak tail current (%WT) V0.5 act V0.5 inact Rec. inact. (%WT) Deactivation (%WT)
22517356 2012 Xeno

H485Q Reported Functional Data: homozygously collected

PMID Year Cell type S.S. peak current (%WT) Peak tail current (%WT) V0.5 act V0.5 inact Rec. inact. (%WT) Deactivation (%WT)
22517356 2012 Xeno 13 -10.50

H485Q 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
1 0.581 -5.552 0.236 2

H485Q has 29 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
8 14.2
9 13.9 A9T A9V
398 8.6 W398L W398X
399 7.7
400 10.3 I400N
401 11.5
402 13.8 H402R
469 14.4
470 14.1 N470D
471 11.6 F471X
472 8.1 R472C R472X
473 10.1 T473P
474 9.3 T474I
475 10.8 Y475C Y475Del
476 14.4 V476I
477 14.5
480 13.6 E480V
481 14.1
482 10.7 V482A
483 7.7 V483I
484 4.1
486 5
487 6.9 G487R G487S
488 6.6 R488C R488H
489 7.9 I489F I489I
490 10.9 A490P A490T
491 12.7 V491I
492 13.8 H492Y
493 14.9 Y493C Y493F Y493H Y493Ins