Long QT syndrome

Gene: KCNE1

Green List (high evidence)

KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000180509
EnsemblGeneIds (GRCh37): ENSG00000180509
OMIM: 176261, Gene2Phenotype
KCNE1 is in 9 panels

10 reviews

Zornitza Stark (Australian Genomics)

I don't know

Please note recent LIMITED assessment by ClinGen LQTS Working Group:
Genetic evidence associating this gene with disease causality was based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS. Studies in large families with variant
segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS (rated as MODERATE).
Created: 1 Jun 2020, 10:35 a.m. | Last Modified: 1 Jun 2020, 10:35 a.m.
Panel Version: 2.6

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Jervell and Lange-Nielsen syndrome 2, MIM# 612347; Long QT syndrome 5, MIM# 613695

Publications

Claire Kirk (UCD)

This is just a query about the Long QT panel in general. Panel app lists all of the green Long QT genes as completely penetrant. I thought the 3 strongest genes (LQTS1-3) were only 50-60% penetrant at most?
Created: 2 Apr 2020, 9:23 a.m. | Last Modified: 2 Apr 2020, 9:23 a.m.
Panel Version: 2.5

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Penetrance for this gene has been changed from "complete" to "incomplete" based on PMID: 11692163 and also review from Claire Kirk (UCD).
Created: 12 Jun 2020, 2:18 p.m. | Last Modified: 12 Jun 2020, 2:18 p.m.
Panel Version: 2.16
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
Comment on mode of inheritance: MOI was corrected.
Created: 30 Sep 2019, 12:51 p.m. | Last Modified: 30 Sep 2019, 12:51 p.m.
Panel Version: 1.40

Rebecca Whittington (South West GLH)

Green List (high evidence)

Jervell and Lange-Nielsen syndrome 2 (OMIM 612347 - AR), Long QT syndrome 5 (OMIM 613695 - AD)
Created: 25 Mar 2019, 4:30 p.m.
Lots of literature evidence for this gene. Possible milder phenotype. PMID:19716085. PMID: 17341399. PMID: 14499862.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Green List (high evidence)

Gene on Royal Brompton diagnostic panel.
Created: 19 Mar 2019, 3:06 p.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Jervell and Lange-Nielsen syndrome 2 (612347); Long QT syndrome-5 (613695)

Publications

James Eden (Manchester)

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 49 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: currently no stated association with LQT, moderate association with Jervell and Lange-Nielsen syndrome 2 (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
Jervell and Lange-Nielsen syndrome 2 (612347); Long QT syndrome-5 (613695)

Publications

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

Bill Newman (Manchester Centre for Genomic Medicine)

Green List (high evidence)

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.
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). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 40.
Created: 19 Feb 2016, 10:41 a.m.

Damian Smedley (Genomics England Curator)

Comment on mode of inheritance: Biallelelic mutations cause JERVELL AND LANGE-NIELSEN SYNDROME 2; JLNS2 (OMIM:612347) where long QT is one of the phenotypes
Created: 29 Jan 2016, 12:51 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Expert list
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Long QT syndrome 5 (613695)
  • Jervell and Lange-Nielsen syndrome 2 (612347)
Tags
for-review
OMIM
176261
Clinvar variants
Variants in KCNE1
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

12 Jun 2020, Gel status: 3

Removed Source, Removed Source, Removed Source, Set penetrance

Ivone Leong (Genomics England Curator)

Source South West GLH was removed from KCNE1. Source London South GLH was removed from KCNE1. Source North West GLH was removed from KCNE1. Penetrance for gene KCNE1 was set from to Complete

12 Jun 2020, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KCNE1 were set to 19716085; 31983240

12 Jun 2020, Gel status: 3

Added Tag

Ivone Leong (Genomics England Curator)

Tag for-review tag was added to gene: KCNE1.

12 Jun 2020, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KCNE1 were set to 19716085

30 Sep 2019, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: KCNE1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

12 Sep 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: KCNE1 were changed from Long QT syndrome-5 (613695); Long QT syndrome-5 ; Jervell and Lange-Nielsen syndrome 2 (612347) to Long QT syndrome 5 (613695); Jervell and Lange-Nielsen syndrome 2 (612347)

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 KCNE1. Mode of inheritance for gene KCNE1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to KCNE1.

14 Feb 2019, Gel status: 3

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

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to KCNE1. Added phenotypes Long QT syndrome-5 (613695); Jervell and Lange-Nielsen syndrome 2 (612347) for gene: KCNE1 Publications for gene KCNE1 were changed from to 19716085 Rating Changed from Green List (high evidence) to Green List (high evidence)

29 Jan 2016, Gel status: 4

Gene classified by Genomics England curator

Damian Smedley (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

29 Jan 2016, Gel status: 4

Set Mode of Inheritance

Damian Smedley (Genomics England Curator)

Mode of inheritance for KCNE1 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

13 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE1 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE1 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE1 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE1 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE1 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN,Expert list,Emory Genetics Laboratory