I500Del Summary

KCNH2 I500Del was found in 1 paper (see below) with a total of 5 carriers: 5 had LQT2. I500Del is not present in gnomAD. I500Del has been functionally characterized in 1 paper. Given the functional data available, we estimate this variant has "LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). 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.

I500Del Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
7889573 1995 11 0 5
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

I500Del 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)
8700910 1996 Xeno 50.6 3

I500Del 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)
8700910 1996 Xeno 0

I500Del 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

I500Del has 36 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
418 14
421 14.6 T421fsX T421M
463 11.8 F463L
464 14 I464X
466 12.6 D466E
467 11.3
470 12.9 N470D
471 14.7 F471X
492 14.1 H492Y
493 10.2 Y493C Y493F Y493H Y493Ins
494 11.9 F494Del
495 11.4 K495X
496 7.7
497 6.6 W497L W497X
498 7
499 4.5
501 4.6 D501H D501N D501Y
502 6.1 M502I
503 6
504 7.6 A504V
505 10 A505V
506 11.1 I506V
507 14.9 P507L P507S
526 13.1
527 9.4
528 12.7 R528P R528W R528X
529 10.8
530 5.7
531 9.6 R531Del R531Q R531W
532 10.5
533 7
534 8.4 R534C
535 12.6 V535M
536 11.7 A536X
537 9.7 R537W
538 13.3