Long QT syndrome

Gene: KCNJ5

Red List (low evidence)

KCNJ5 (potassium voltage-gated channel subfamily J member 5)
EnsemblGeneIds (GRCh38): ENSG00000120457
EnsemblGeneIds (GRCh37): ENSG00000120457
OMIM: 600734, Gene2Phenotype
KCNJ5 is in 5 panels

9 reviews

Ivone Leong (Genomics England Curator)

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.
Created: 18 Nov 2019, 2:09 p.m. | Last Modified: 18 Nov 2019, 2:09 p.m.
Panel Version: 1.44

James Eden (Manchester)

I don't know

Gene currently tested on Manchester cardiac gene panel. 16 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: gene not curated (accessed 29/01/2019).
Created: 19 Sep 2019, 9:53 a.m. | Last Modified: 19 Sep 2019, 9:53 a.m.
Panel Version: 1.38

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Long QT syndrome 13 (613485); Hyperaldosteronism, familial, type III (613677)

Publications

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

Rebecca Whittington (South West GLH)

Green List (high evidence)

Hyperaldosteronism, familial, type III (OMIM 613677), Long QT syndrome 13 (OMIM 613485).
Created: 25 Mar 2019, 4:30 p.m.
Literature evidence includes a large Chinese Pedigree. PMID:20560207. PMID:25322277. PMID: 24574546.
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

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

Red List (low evidence)

Gene currently on Royal Brompton diagnostic panel, only a few VUS reported. Low literature evidence based on small number of cases (mainly Wang et al. (2013) Heart Rhythm 10:1500-1506).
Created: 19 Mar 2019, 4:06 p.m. | Last Modified: 19 Sep 2019, 9:15 a.m.
Panel Version: 1.38

Bill Newman (Manchester Centre for Genomic Medicine)

Green List (high evidence)

Caroline Wright (Genomics England Curator)

Comment on list classification: On Manchester diagnostic panel
Created: 7 Mar 2016, 4:25 p.m.

Ellen McDonagh (Genomics England Curator)

I don't know

Comment on list classification: Due to limited evidence for causation of Long QT syndrome, the decision was made to demote this gene from Green to Red in the NHSE GMS Cardiology Specialist Group meeting call on 25th January 2019.
Created: 4 Mar 2019, 9:09 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 for Long QT syndrome 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 = 1.
Created: 19 Feb 2016, 11:04 a.m.

Damian Smedley (Genomics England Curator)

Comment when marking as ready: Good evidence from OMIM as well
Created: 1 Feb 2016, 9:02 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

This gene is linked to LQTS based on a large Chinese family with the p.Gly387Arg variant (Wang et al. (2013) HeartRhythm 10:1500_1506 Yang et al. 2010 American Journal of Human Genetics 86:872-880). However this variant is present in 47 out of 9424 South Asians in GnomAD (0.5 percent). Oxford lab classify as VUS. Therefore no evidence to support that variants in this gene cause LQTS.
Created: 25 Jan 2019, 12:41 p.m.
1 large 4 generational chinese family reported to have a variant in this gene; however, that variant is present in 0.4% of East Asian individuals on ExAC. Other reported variants appear to be associated with hyperaldosteronism.
Created: 3 Mar 2016, 9:13 a.m.

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hyperaldosteronism, familial, type III (613677)
  • Long QT syndrome 13 (613485)
  • Long QT syndrome 13
OMIM
600734
Clinvar variants
Variants in KCNJ5
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

4 Mar 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: kcnj5 has been classified as Red List (Low Evidence).

4 Mar 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: kcnj5 has been classified as Red List (Low Evidence).

21 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to KCNJ5.

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to KCNJ5.

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 KCNJ5. Added phenotypes Hyperaldosteronism, familial, type III (613677); Long QT syndrome 13 (613485) for gene: KCNJ5 Publications for gene KCNJ5 were changed from to 19716085 Rating Changed from Green List (high evidence) to Green List (high evidence)

7 Mar 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

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

7 Mar 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

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

4 Mar 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

1 Feb 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).

1 Feb 2016, Gel status: 3

Set Mode of Inheritance

Damian Smedley (Genomics England Curator)

Mode of inheritance for KCNJ5 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNJ5 was added to Long QT syndromepanel. Sources: UKGTN

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNJ5 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNJ5 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Expert list

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNJ5 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNJ5 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNJ5 was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Expert list