E365R Summary

KCNH2 E365R was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. E365R is not present in gnomAD. E365R has been functionally characterized in 1 paper. 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.


E365R 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.

E365R 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)
16997865 2006 HEK293

E365R 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)
16997865 2006 HEK293 17.00

E365R 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
-9 NA NA NA NA

E365R 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
350 14.7
351 14.2 S351L
352 13.7
353 13.2 T353S
354 12.6
355 12 D355G
356 11.4 R356C R356H
357 10.7 E357D
358 10.1
359 9.3 I359V
360 8.5
361 7.6
362 6.6
363 5.4 I363X
364 3.8 K364X
366 3.8 R366Q R366X
367 5.4 T367S
368 6.6 H368Y
369 7.6 N369K
370 8.5
371 9.3
372 10.1
373 10.7
374 11.4
375 12
376 12.6 Q376R Q376sp
377 13.2
378 13.7
379 14.2 S379Y
380 14.7 L380X