I458S Summary

KCNH2 I458S was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I458S is not present in gnomAD. I458S has been functionally characterized in 0 papers. 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 2 individuals unaffected with LQT2 and 8 individuals affected with LQT2.


I458S 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.

I458S 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
NA 0.905 -5.252 0.992 -3

I458S has 33 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 13.4 W410X
413 11.8 L413P
414 12.8 I414fsX
416 12.6
417 9.3
418 13.2
419 14.8
420 9.7 Y420C
421 12.1 T421fsX T421M
424 13.1
425 14.7
449 14
450 13.5
451 11.6 P451L
452 10.7
453 8.8
454 6.5
455 5.2
456 6.6 D456Y
457 4.9 L457P
459 4.7
460 6.5 D460fsX
461 5.5
462 6.8 M462Ins
463 9.8 F463L
464 10.6 I464X
465 10.9
466 13.5 D466E
504 14.2 A504V
505 13.3 A505V
507 13.1 P507L P507S
528 12.3 R528P R528W R528X
531 12.5 R531Del R531Q R531W