E435A Summary

KCNH2 E435A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. E435A is not present in gnomAD. E435A has been functionally characterized in 1 paper. This residue is located in a Non_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.

E435A 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.

E435A 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)
22573844 2012 HEK293

E435A 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)
22573844 2012 HEK293 2.00 -2.00 110.6

E435A 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 0.754 -4.001 0.65 -1

E435A has 30 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
420 14.7 Y420C
421 14.2 T421fsX T421M
422 13.7 A422T
423 13.2
424 12.6
425 12
426 11.4 P426H
427 10.7 Y427C Y427H Y427S
428 10.1 S428fsX S428L S428X
429 9.3 A429P A429V
430 8.5
431 7.6 F431L
432 6.6
433 5.4
434 3.8
436 3.8 T436M
437 5.4
438 6.6 E438K E438X
439 7.6
440 8.5 P440L
441 9.3 P441L P441R
442 10.1
443 10.7 T443fsX T443N
444 11.4 E444D E444K
445 12
446 12.6
447 13.2 Y447X
448 13.7 A448S A448T
449 14.2
450 14.7