G572S Summary

KCNH2 G572S was found in 21 papers (see below) with a total of 38 carriers: 36 had LQT2. G572S is not present in gnomAD. G572S has been functionally characterized in 2 papers. Given the functional data available, we estimate this variant has "Severe Dominant 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 2 individuals unaffected with LQT2 and 8 individuals affected with LQT2.


G572S Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
0 1
15176425 2004 2 0 2
15840476 2005 2 0 2
17905336 2007 1 0 1
19038855 2009 1 0 1 Seizure
19306396 2009 3 0 3
19490267 2009 1 0 1
19996378 2009 1 0 1
20197117 2010 4 0 2
21063070 2010 1 0 1
21216356 2011 1 0 1
21308345 2010 5 1 4
22727609 2012 1 0 1
24217263 2013 1 0 congenital LQT
26496715 2015 2 0 2
27871843 2017 1 0 1
28532774 2017 1 0 1
29622001 2018 2 0 2
29650123 2018 1 0
Japan Cohort 2020 12 1 11
Paris Cohort 2020 3 0 3
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G572S 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)
19490267 2009 HEK293 11.1
28082916 2016 HEK293

G572S 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)
19490267 2009 HEK293
28082916 2016 HEK293 16 0.00 211.1

G572S 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
-2 0.959 -5.632 0.999 0

G572S 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