E544G Summary

KCNH2 E544G was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. E544G is not present in gnomAD. E544G 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 3 individuals unaffected with LQT2 and 7 individuals affected with LQT2.


E544G 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.

E544G 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)
24407947 2014 Xeno

E544G 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)
24407947 2014 Xeno -0.80

E544G 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
-4 0.939 -6.704 0.975 -2

E544G has 49 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
3 7.1
4 12.3
5 12.8
402 13.5 H402R
403 13.5
404 13.8
405 13.5
407 13.8
408 10.3
409 12.7 V409L V409M
411 11.7
412 9.7 W412X
415 14
535 13.7 V535M
536 14.4 A536X
538 12
539 9.6
540 6.6 D540fsX
541 6.6 R541C R541H
542 7.9
543 5.1 S543fsX
545 4.7
546 8.2
547 10.1 A547T
548 8.7
549 9.5 V549M
550 13.7
551 13.9 F551L
552 12.7 L552S
662 13.6
665 12.1 R665Q
666 13.5
670 13.6
671 14.4 A671Del A671G
673 10.9
674 8.9 H674fsX H674Y
675 13.1
676 14.7 Q676fsX Q676X
677 9.1 M677T
678 10
680 12.5
681 7.6 R681W
682 13.5 E682X
684 13.8
685 12.4 R685C R685H R685P
694 13.1 R694C R694H
698 11.4 E698K E698X
701 14
702 12.3