Short QT syndrome
Gene: KCNH2
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
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
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.
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
Just 1 variant reportedly in a SQTS family (N588K).Created: 25 Jan 2019, 12:52 p.m.
Gain of function variants associated with Short QT in OMIM and not in Gen2Phen. At least 3 variants identified in 5 unrelated casesCreated: 15 Nov 2018, 12:10 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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: LiteratureCreated: 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
Source West Midlands, Oxford and Wessex GLH was added to KCNH2.
Publications for gene: KCNH2 were set to 16226079; 16301704
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
Source London South GLH was added to KCNH2.
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
Jules Hancox: First gene implicated in short
Publications for gene: KCNH2 were set to PMID:14676148; 15828882; 19340359; 18692916; 21130771; 25974115; 29016797; 29759541; 16011830; 19439805; 22194679; 16039272; 29085299
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)
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