G446R Summary

KCNH2 G446R was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. G446R is not present in gnomAD. G446R has been functionally characterized in 0 papers. This residue is located in a Mild_Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 7 individuals unaffected with LQT2 and 3 individuals affected with LQT2.


G446R 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.

G446R 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 0.729 -5.715 0.999 -2

G446R has 30 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
431 14.7 F431L
432 14.2
433 13.7
434 13.2
435 12.6 E435G E435X
436 12 T436M
437 11.4
438 10.7 E438K E438X
439 10.1
440 9.3 P440L
441 8.5 P441L P441R
442 7.6
443 6.6 T443fsX T443N
444 5.4 E444D E444K
445 3.8
447 3.8 Y447X
448 5.4 A448S A448T
449 6.6
450 7.6
451 8.5 P451L
452 9.3
453 10.1
454 10.7
455 11.4
456 12 D456Y
457 12.6 L457P
458 13.2
459 13.7
460 14.2 D460fsX
461 14.7