Long QT syndrome
Gene: KCNE2
Please note recent assessment by ClinGen: KCNE2 was concluded to have strong evidence for acquired LQTS, however a recent comprehensive review of reported KCNE2 variants reported for LQTS demonstrated that KCNE2 variants routinely require secondary provocation to induce phenotype, persuading the Working Group to conclude that KCNE2 has no supportive evidence as a cause of LQTS in the absence of provoking factors (PMID: 28794082).Created: 1 Jun 2020, 10:42 a.m. | Last Modified: 1 Jun 2020, 10:42 a.m.
Panel Version: 2.6
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Long QT syndrome 6, MIM# 613693
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 11:51 a.m. | Last Modified: 3 Mar 2022, 11:51 a.m.
Panel Version: 2.31
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, 2:09 p.m. | Last Modified: 18 Nov 2019, 2:09 p.m.
Panel Version: 1.44
Atrial fibrillation, familial, 4 (OMIM 611493), Long QT syndrome 6 (OMIM 613693)Created: 25 Mar 2019, 4:30 p.m.
Literature/functional evidence for this gene. PMID:19716085. PMID:27465075. PMID:20042375.Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
On Royal Brompton diagnostic LQTS panel. Decent evidence in literature; however ony VUS reported from our lab so far, and no definitive pathogenic ClinVar entries.Created: 19 Mar 2019, 3:12 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Long QT syndrome-6 (613693); Atrial fibrillation, familial, 4 (611493)
Gene currently tested on Manchester cardiac gene panel. 25 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: gene not curated (accessed 29/01/2019).Created: 14 Feb 2019, 1:38 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Long QT syndrome-6 (613693); Atrial fibrillation, familial, 4 (611493)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: On Manchester diagnostic panelCreated: 7 Mar 2016, 4:17 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.
On the Inherited Cardiac Condition Genes panel reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.1007/s12265-016-9673-5). This gene was within the list categorised by primary disease association. No. of mutations indicated in supplemental table = 22.
Created: 4 Mar 2016, 4:25 p.m.
Publications
Comment when marking as ready: Good evidence from OMIM as wellCreated: 1 Feb 2016, 9:01 p.m.
Very little genetic variation in this gene. No significant evidence of pathogenic variants in this gene according to todays classification standards but it remains a good functional candidate. Happy for it to remain on the LQT panel.Created: 25 Jan 2019, 12:41 p.m.
Traditionally considered a LQTS causing gene, however, no KCNE2 variants detected in our cohort have been classified as 'pathogenic'. Lots of variants detected in this gene at relatively low levels on ExAC. Whole gene deletions (including the region that covers KCNE1) have been detected in our cohort.Created: 2 Mar 2016, 4:20 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: KCNE2.
Source Expert Review Amber was added to KCNE2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Tag for-review tag was added to gene: KCNE2.
Phenotypes for gene: KCNE2 were changed from Long QT syndrome-6 (613693); Long QT syndrome-6 ; Atrial fibrillation, familial, 4 (611493) to Long QT syndrome 6 (613693); Atrial fibrillation, familial, 4 (611493)
Publications for gene: KCNE2 were set to 19716085
Source South West GLH was added to KCNE2.
Source London South GLH was added to KCNE2.
Source North West GLH was added to KCNE2. Added phenotypes Long QT syndrome-6 (613693); Atrial fibrillation, familial, 4 (611493) for gene: KCNE2 Publications for gene KCNE2 were changed from to 19716085 Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Green List (High Evidence).
Mode of inheritance for KCNE2 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Model of inheritance for gene KCNE2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
KCNE2 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory
Model of inheritance for gene KCNE2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
KCNE2 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory
Model of inheritance for gene KCNE2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
KCNE2 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory
Model of inheritance for gene KCNE2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
KCNE2 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory
KCNE2 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory