A527W Summary

KCNH2 A527W was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. A527W is not present in gnomAD. A527W 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.

A527W 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.

A527W 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

A527W 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 1.20 100

A527W 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

A527W has 43 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
417 14.2
418 12.1
419 14.8
420 13.3 Y420C
421 9.3 T421fsX T421M
422 10.8 A422T
423 13.7
424 14
425 8.5
426 10.8 P426H
428 12.7 S428fsX S428L S428X
429 11.8 A429P A429V
430 14.7
456 12.8 D456Y
459 12.9
460 11.1 D460fsX
463 11.1 F463L
464 14.1 I464X
498 14.2
499 12.3
500 9.4 I500Del
501 10.3 D501H D501N D501Y
502 9.7 M502I
503 6.2
504 5.9 A504V
505 9 A505V
506 8.3 I506V
507 10.2 P507L P507S
508 10.2
521 13.1
522 10.4 G522E
523 9.4
524 7.1
525 7.1 K525N
526 4.2
528 5.1 R528P R528W R528X
529 5.4
530 5.2
531 6.9 R531Del R531Q R531W
532 10.5
533 11
534 12.1 R534C
563 13 W563C W563G W563X