D460A Summary

KCNH2 D460A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. D460A is not present in gnomAD. D460A 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.


D460A 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.

D460A 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)
15975984 2005 Xeno

D460A 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)
15975984 2005 Xeno 22.30 7.60

D460A 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 0.98 -7.413 0.999 -2

D460A 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
410 14.4 W410X
413 13.9 L413P
414 12.5 I414fsX
416 14.3
417 9.5
418 11.6
419 14.4
420 9.9 Y420C
421 9.6 T421fsX T421M
422 13.7 A422T
423 14.9
424 12.8
425 11.5
428 14.2 S428fsX S428L S428X
452 12.5
453 10.1
454 10.2
455 9.2
456 5.9 D456Y
457 5.1 L457P
458 6.5
459 4.3
461 5.2
462 7.6 M462Ins
463 6.4 F463L
464 7 I464X
465 10
466 11.3 D466E
467 11.9
468 13.8 L468F L468R L468X
501 12.7 D501H D501N D501Y
502 12.1 M502I
503 11.7
504 8.1 A504V
505 7.2 A505V
506 9.2 I506V
507 7.2 P507L P507S
508 10.9
509 13.6 D509N
524 13.6
525 10.2 K525N
526 13.4
527 11.1
528 7 R528P R528W R528X
529 13
530 13
531 7.9 R531Del R531Q R531W
532 14.9
534 12.9 R534C