A536W Summary

KCNH2 A536W was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. A536W is not present in gnomAD. A536W 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 5 individuals unaffected with LQT2 and 5 individuals affected with LQT2.


A536W 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.

A536W 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)
16166152 2005 Xeno

A536W 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)
16166152 2005 Xeno -64.40 100

A536W 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
-13 NA NA NA NA

A536W has 41 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 13.5
411 11.4
412 13.2 W412X
414 11.8 I414fsX
415 10.6
417 14.8
418 11.3
419 13.6
421 14.9 T421fsX T421M
422 14.6 A422T
463 14.7 F463L
466 14.3 D466E
470 14.6 N470D
493 14.9 Y493C Y493F Y493H Y493Ins
496 13.1
497 8.6 W497L W497X
500 11.7 I500Del
501 11.6 D501H D501N D501Y
529 13.3
530 11.4
531 12.8 R531Del R531Q R531W
532 7.3
533 5.5
534 8.1 R534C
535 4.1 V535M
537 5.5 R537W
538 6.1
539 5.2
540 8.7 D540fsX
541 11.1 R541C R541H
542 8.4
543 10.9 S543fsX
544 14.4 E544A E544fsX
548 14.6
549 13.3 V549M
552 11.1 L552S
553 13.4 L553V
555 14.1
556 12.8
667 13.5 Y667X
670 14