I419M Summary

KCNH2 I419M was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. I419M is not present in gnomAD. I419M 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 3 individuals unaffected with LQT2 and 7 individuals affected with LQT2.


I419M 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.

I419M 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 0.78 -2.68 0.598 1

I419M has 53 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
411 13.1
412 11.5 W412X
413 10.3 L413P
414 9.3 I414fsX
415 6.1
416 5.5
417 6.6
418 4.5
420 6.7 Y420C
421 6.2 T421fsX T421M
422 5.6 A422T
423 6.4
424 8.9
425 10.6
426 11.7 P426H
427 13.8 Y427C Y427H Y427S
428 14.7 S428fsX S428L S428X
455 13.6
456 12.9 D456Y
458 14.8
459 11.2
460 14.4 D460fsX
462 13.7 M462Ins
463 12.2 F463L
527 14.8
528 12.3 R528P R528W R528X
529 10.6
530 13.5
531 10.2 R531Del R531Q R531W
532 8.4
533 12.7
534 12.2 R534C
535 10 V535M
536 13.6 A536X
538 14.1
539 14.8
542 12.1
548 13.9
549 14.9 V549M
551 9.7 F551L
552 9.6 L552S
553 13.2 L553V
554 12.9
555 7.4
556 9.3
557 13.6
558 9.9 A558E A558P A558V
559 7.4 L559F L559H
560 12.3 I560fsX I560M
561 13.3 A561P A561T A561V
562 10.6 H562P H562Q H562R
563 10.6 W563C W563G W563X