Short QT syndrome

Gene: KCNQ1

Green List (high evidence)

KCNQ1 (potassium voltage-gated channel subfamily Q member 1)
EnsemblGeneIds (GRCh38): ENSG00000053918
EnsemblGeneIds (GRCh37): ENSG00000053918
OMIM: 607542, Gene2Phenotype
KCNQ1 is in 11 panels

9 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)

I don't know

Short QT syndrome 2
Created: 25 Mar 2019, 4:30 p.m.
2 reported variants on HGMD 15159330 , with functional studies 26168993, 28814790
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

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.

James Eden (Manchester)

Green List (high evidence)

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

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Green List (high evidence)

Small number of cases reported. This would be the main gene to be screened.
Created: 25 Jan 2019, 12:52 p.m.

Louise Daugherty (Genomics England Curator)

Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Created: 19 Nov 2018, 12:26 p.m.

Olivia Niblock (Genomics England Curator)

I don't know

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

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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

Jules Hancox (University of Bristol)

Green List (high evidence)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • West Midlands, Oxford and Wessex GLH
  • Expert Review Green
  • South West GLH
  • London South GLH
  • North West GLH
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Long QT syndrome (Version 1.5)
  • Emory Genetics Laboratory
Phenotypes
  • 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)
OMIM
607542
Clinvar variants
Variants in KCNQ1
Penetrance
unknown
Publications
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 KCNQ1.

12 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KCNQ1 were set to 16226079; 16301704

4 Mar 2019, Gel status: 3

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: kcnq1 has been classified as Green List (High Evidence).

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 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

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to KCNQ1.

14 Feb 2019, Gel status: 4

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

Ellen McDonagh (Genomics England Curator)

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

20 Nov 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Jules Hancox: Gain of function mutations in

19 Nov 2018, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

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

19 Nov 2018, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: KCNQ1 were set to 15159330

15 Nov 2018, Gel status: 3

Added New Source, Added New Source, Added New Source, Added New Source, Added New Source, Set Phenotypes, Status Update

Sarah Leigh (Genomics England Curator)

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)

6 Nov 2017, Gel status: 0

Added New Source

Reviewer Test (Testing)

KCNQ1 was added to Short QT syndrome panel. Sources: Other

6 Nov 2017, Gel status: 0

Created

Reviewer Test (Testing)

KCNQ1 was created by Reviewer Test