F463Y Summary

KCNH2 F463Y was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. F463Y is not present in gnomAD. F463Y 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 4 individuals unaffected with LQT2 and 6 individuals affected with LQT2.


F463Y 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.

F463Y 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

F463Y 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 39.90

F463Y 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
2 0.936 -2.78 1 3

F463Y has 58 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
407 13.5
410 9.6 W410X
411 11.6
413 10.2 L413P
414 7.3 I414fsX
415 11.2
416 11.6
417 6.9
418 8.1
419 12.2
420 10.8 Y420C
421 9 T421fsX T421M
422 12.7 A422T
424 14.7
425 13.2
455 12.9
456 10.6 D456Y
457 11 L457P
458 9.8
459 6
460 6.4 D460fsX
461 7.3
462 5.5 M462Ins
464 6.1 I464X
465 7.2
466 5.8 D466E
467 7.7
468 10.7 L468F L468R L468X
469 10.6
470 10.8 N470D
471 13.9 F471X
493 13.5 Y493C Y493F Y493H Y493Ins
497 14.2 W497L W497X
498 12.1
499 14.4
500 11.8 I500Del
501 8 D501H D501N D501Y
502 9.7 M502I
503 10.5
504 6.6 A504V
505 7 A505V
506 10.7 I506V
507 11.2 P507L P507S
508 14.9
525 13.8 K525N
526 14.4
527 11.1
528 8.8 R528P R528W R528X
529 11.7
530 10.3
531 5 R531Del R531Q R531W
532 10.8
533 11.1
534 6.9 R534C
535 12 V535M
536 14.7 A536X
537 12.5 R537W
538 12.4