K538Q Summary

KCNH2 K538Q was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. K538Q is not present in gnomAD. K538Q 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 7 individuals unaffected with LQT2 and 3 individuals affected with LQT2.


K538Q 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.

K538Q 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)
23980197 2013 Xeno

K538Q 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)
23980197 2013 Xeno -37.90

K538Q 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
-3 0.921 -3.834 0.999 1

K538Q has 56 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 9.8
4 13.1
401 14.8
402 10.9 H402R
403 14.5
404 13.6
405 14.9
406 14.1
407 8.9
408 9.9
409 12.2 V409L V409M
410 10.5 W410X
411 6.1
412 9.7 W412X
413 12 L413P
414 8.3 I414fsX
415 9
416 13.6
417 12.8
418 11.1
419 14.1
462 14.7 M462Ins
463 12.4 F463L
466 10.2 D466E
467 13.3
469 12.4
470 10.1 N470D
473 12.1 T473P
474 12.9 T474I
475 13.1 Y475C Y475Del
476 12.8 V476I
492 14.1 H492Y
493 12.4 Y493C Y493F Y493H Y493Ins
496 13.5
497 9.5 W497L W497X
498 14.4
500 13.3 I500Del
501 11 D501H D501N D501Y
530 13.8
531 12.9 R531Del R531Q R531W
532 10.1
533 8.5
534 6.6 R534C
535 5.3 V535M
536 6.1 A536X
537 4.4 R537W
539 6.6
540 7.1 D540fsX
541 6.5 R541C R541H
542 6.3
543 10.7 S543fsX
544 12 E544A E544fsX
545 14.7
548 14.2
549 14.4 V549M
552 12.7 L552S