G572D Summary

KCNH2 G572D was found in 1 paper (see below) with a total of 3 carriers: 2 had LQT2. G572D is not present in gnomAD. G572D 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.


G572D Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
Japan Cohort 2020 3 1 2
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G572D 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
-3 0.97 -6.597 0.998 -2

G572D has 50 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
429 14.1 A429P A429V
430 10.8
431 11.1 F431L
432 14.3
564 13.6 L564L
565 11.4
566 11.2 C566F C566G C566R C566S
567 9.9 I567M I567T
568 7.4 W568C
569 6 Y569C Y569H Y569X
570 5.1
571 4.4 I571L I571V
573 3.6
574 6.4 M574L M574V
575 5.7 E575K
576 6.3
577 9.6
583 10 I583V
584 7.9 G584C G584R G584S
585 6.4 W585C
586 6.2 L586M
587 9
588 11.8 N588D N588K
589 11.6 L589P
590 13.5 G590D G590V
597 11.9 Y597C Y597H
603 14.9 G603D
604 14 G604C G604D G604S
605 12.4 P605L
606 14.6 S606Del S606F S606P
607 13.5
609 14 D609G D609N
610 9.9
611 14.1 Y611D
613 12.4 T613A T613K T613L T613M
614 11.2 A614T A614V
617 12.9 F617L F617V
618 14.8 T618S
630 13.1 V630A V630I V630T
631 12.7 S631F
632 11.9 P632A P632S
633 11.7 N633D N633I N633S
634 9.3 T634A T634I T634P T634S
635 12.4 N635I
636 8.9
637 7.9 E637G E637K E637X
638 13.2 K638D K638Del K638E K638R
639 13.6 I639F I639N
640 11.4 F640Del F640L F640V
641 14.4 S641F S641P