D466C Summary

KCNH2 D466C was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. D466C is not present in gnomAD. D466C 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.


D466C 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.

D466C 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)
15545400 2004 Xeno

D466C 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)
15545400 2004 Xeno 41.50

D466C 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
-14 NA NA NA NA

D466C has 61 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
400 12.3 I400N
401 14.6
402 14.1 H402R
404 14.6
406 11.4
407 9
408 12.7
409 13 V409L V409M
410 7 W410X
411 9.1
412 14.1 W412X
413 10.5 L413P
414 7.5 I414fsX
415 12.4
416 13.9
417 10.4
418 11.6
421 14.1 T421fsX T421M
458 13.5
459 10.9
460 11.3 D460fsX
461 9.9
462 7 M462Ins
463 5.8 F463L
464 7 I464X
465 5
467 4.7
468 6.8 L468F L468R L468X
469 5.1
470 5.4 N470D
471 9.2 F471X
472 11.9 R472C R472X
473 9.6 T473P
474 13.2 T474I
489 13.9 I489F I489I
490 14.5 A490P A490T
493 9.8 Y493C Y493F Y493H Y493Ins
494 14.6 F494Del
496 14.5
497 12.6 W497L W497X
498 10.4
499 14.4
500 12.6 I500Del
501 8.1 D501H D501N D501Y
502 10.7 M502I
503 13.2
504 10.3 A504V
505 9.9 A505V
506 13.9 I506V
528 14.3 R528P R528W R528X
530 13.4
531 9.8 R531Del R531Q R531W
532 13.4
533 12.2
534 6.8 R534C
535 12.3 V535M
536 14.3 A536X
537 10.5 R537W
538 10.2
541 14 R541C R541H
542 14.4