Short QT syndrome

Gene: KCNH2

Green List (high evidence)

KCNH2 (potassium voltage-gated channel subfamily H member 2)
EnsemblGeneIds (GRCh38): ENSG00000055118
EnsemblGeneIds (GRCh37): ENSG00000055118
OMIM: 152427, Gene2Phenotype
KCNH2 is in 3 panels

7 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.
Created: 18 Nov 2019, 2:43 p.m. | Last Modified: 18 Nov 2019, 2:43 p.m.
Panel Version: 1.23

Rebecca Whittington (South West GLH)

Green List (high evidence)

Short QT syndrome 2 (609621)
Created: 25 Mar 2019, 4:30 p.m.
Multiple DM variants on HGMD with functional studies.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

James Eden (Manchester)

Green List (high evidence)

Gene currently tested by alternative panel, very few short QT referrals to date. 947 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: currently no association with Short QT syndrome, association with long QT syndrome 2, disputed association with Brugada syndrome 1 (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Long QT syndrome-2 (613688); Short QT syndrome 1 (609620)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Just 1 variant reportedly in a SQTS family (N588K).
Created: 25 Jan 2019, 12:52 p.m.

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Gain of function variants associated with Short QT in OMIM and not in Gen2Phen. At least 3 variants identified in 5 unrelated cases
Created: 15 Nov 2018, 12:10 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Jules Hancox (University of Bristol)

Green List (high evidence)

First gene implicated in short QT syndrome. Responsible for SQTS variant 1

Different mutations have different degrees of penetrance: N588K and T618I are 100% penetrant; some others have incomplete penetrance.

The mutations are gain-of-function mutations that increase cardiac I(Kr) and abbreviate cardiac action potential duration leading to shortened QT intervals

KCNH2 aka hERG (human Ether-a-go-go-Related Gene). Gene product: hERG or Kv11.1
Sources: Literature
Created: 17 Oct 2018, 7:06 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
short qt; atrial fibrillation; ventricular fibrillation; cardiac arrest; Brugada

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • West Midlands, Oxford and Wessex GLH
  • South West GLH
  • London South GLH
  • North West GLH
  • Long QT syndrome (Version 1.5)
  • Brugada syndrome (Version 1.7)
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Brugada
  • Short QT syndrome 1 (609620)
  • ventricular fibrillation
  • cardiac arrest
  • Short QT syndrome 1 609620
  • Long QT syndrome-2 (613688)
  • short qt
  • atrial fibrillation
OMIM
152427
Clinvar variants
Variants in KCNH2
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

13 Sep 2019, Gel status: 3

Added New Source

Ivone Leong (Genomics England Curator)

Source West Midlands, Oxford and Wessex GLH was added to KCNH2.

12 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KCNH2 were set to 16226079; 16301704

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to KCNH2. Mode of inheritance for gene KCNH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to KCNH2.

14 Feb 2019, Gel status: 4

Added New Source, Set Phenotypes, Set publications

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to KCNH2. Added phenotypes Short QT syndrome 1 (609620); Long QT syndrome-2 (613688) for gene: KCNH2 Publications for gene KCNH2 were changed from 14676148; 15828882; 19340359; 18692916; 21130771; 25974115; 29016797; 29759541; 16011830; 19439805; 22194679; 16039272; 29085299 to 16226079; 16301704

20 Nov 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Jules Hancox: First gene implicated in short

19 Nov 2018, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: KCNH2 were set to PMID:14676148; 15828882; 19340359; 18692916; 21130771; 25974115; 29016797; 29759541; 16011830; 19439805; 22194679; 16039272; 29085299

15 Nov 2018, Gel status: 3

Added New Source, Added New Source, Added New Source, Added New Source, Added New Source, Added New Source, Set mode of inheritance, Set Phenotypes, Status Update

Sarah Leigh (Genomics England Curator)

Source UKGTN was added to KCNH2. Source Radboud University Medical Center, Nijmegen was added to KCNH2. Source Emory Genetics Laboratory was added to KCNH2. Source Expert Review Green was added to KCNH2. Source Brugada syndrome (Version 1.7) was added to KCNH2. Source Long QT syndrome (Version 1.5) was added to KCNH2. Mode of inheritance for gene KCNH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Short QT syndrome 1 609620 for gene: KCNH2 Rating Changed from No List (delete) to Green List (high evidence)

17 Oct 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Jules Hancox (University of Bristol)

gene: KCNH2 was added gene: KCNH2 was added to Short QT syndrome. Sources: Literature Mode of inheritance for gene: KCNH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNH2 were set to PMID:14676148; 15828882; 19340359; 18692916; 21130771; 25974115; 29016797; 29759541; 16011830; 19439805; 22194679; 16039272; 29085299 Phenotypes for gene: KCNH2 were set to short qt; atrial fibrillation; ventricular fibrillation; cardiac arrest; Brugada Mode of pathogenicity for gene: KCNH2 was set to Other Review for gene: KCNH2 was set to GREEN