Short QT syndrome
Gene: KCNQ1
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 2Created: 25 Mar 2019, 4:30 p.m.
2 reported variants on HGMD 15159330 , with functional studies 26168993, 28814790Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment when marking as ready: Confirmed in the NHSE GMS Cardiology Specialist Group meeting call on 25th January 2019 that this gene should be Green.Created: 4 Mar 2019, 9:15 p.m.
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. 643 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: currently no association with Short QT syndrome, definitive association with Jervell and Lange-Nielsen syndrome, association with long QT syndrome 1 (accessed 29/01/2019).Created: 14 Feb 2019, 1:38 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Long QT syndrome-1 (192500); Short QT syndrome 2 (609621); Jervell and Lange-Nielsen syndrome (220400); Atrial fibrillation, familial, 3 (607554)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Small number of cases reported. This would be the main gene to be screened.Created: 25 Jan 2019, 12:52 p.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to GreenCreated: 19 Nov 2018, 12:26 p.m.
This has been added as part of a test of the new version of PanelApp. However, variants in this gene do appear to be linked to Short QT-interval Syndrome 2, from the cases (5 individuals) described in OMIM. More literature mining is needed.
Originally stated: 6 Nov 2017, 11:47 a.m.Created: 15 Nov 2018, 1:41 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Idiopathic Ventricular Fibrillation; Short QT-interval syndrome
Publications
Gain of function variants associated with the Short QT phenotype 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
Gain of function mutations in KCNQ1 increase cardiac I(Ks).Created: 17 Oct 2018, 6:49 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
short qt; atrial fibrillation; sinus bradycardia
Publications
Mode of pathogenicity
Other
Phenotypes for gene: KCNQ1 were changed from Short QT syndrome 2 609621; Long QT syndrome-1 (192500); Atrial fibrillation, familial, 3 (607554); Short QT syndrome 2 (609621); Idiopathic Ventricular Fibrillation; Short QT-interval syndrome; Jervell and Lange-Nielsen syndrome (220400) to Short QT syndrome 2, OMIM:609621; Long QT syndrome-1, OMIM:192500; Atrial fibrillation, familial, 3, OMIM:607554
Source West Midlands, Oxford and Wessex GLH was added to KCNQ1.
Publications for gene: KCNQ1 were set to 16226079; 16301704
Gene: kcnq1 has been classified as Green List (High Evidence).
Source South West GLH was added to KCNQ1. Mode of inheritance for gene KCNQ1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Source London South GLH was added to KCNQ1.
Source North West GLH was added to KCNQ1. Mode of inheritance for gene KCNQ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Added phenotypes Atrial fibrillation, familial, 3 (607554); Jervell and Lange-Nielsen syndrome (220400); Long QT syndrome-1 (192500); Short QT syndrome 2 (609621) for gene: KCNQ1 Publications for gene KCNQ1 were changed from 15159330; 16109388; 26168993; 26346102; 25974115; 29697308 to 16226079; 16301704
Jules Hancox: Gain of function mutations in
Phenotypes for gene: KCNQ1 were changed from b; Idiopathic Ventricular Fibrillation; Short QT-interval syndrome; Short QT syndrome 2 609621 to Idiopathic Ventricular Fibrillation; Short QT-interval syndrome; Short QT syndrome 2 609621
Publications for gene: KCNQ1 were set to 15159330
Source Emory Genetics Laboratory was added to KCNQ1. Source Long QT syndrome (Version 1.5) was added to KCNQ1. Source Expert Review Green was added to KCNQ1. Source UKGTN was added to KCNQ1. Source Radboud University Medical Center, Nijmegen was added to KCNQ1. Added phenotypes Short QT syndrome 2 609621 for gene: KCNQ1 Rating Changed from No List (delete) to Green List (high evidence)
KCNQ1 was added to Short QT syndrome panel. Sources: Other
KCNQ1 was created by Reviewer Test