Brugada syndrome

Gene: KCNE3

Red List (low evidence)

KCNE3 (potassium voltage-gated channel subfamily E regulatory subunit 3)
EnsemblGeneIds (GRCh38): ENSG00000175538
EnsemblGeneIds (GRCh37): ENSG00000175538
OMIM: 604433, Gene2Phenotype
KCNE3 is in 4 panels

5 reviews

Rebecca Whittington (South West GLH)

I don't know

?Brugada syndrome 6 (OMIM 613119)
Created: 25 Mar 2019, 4:30 p.m.
Reported in Japanese patient with ?apparent functional effect but also recorded 36x on GnomAD and not strong BI. Also variant in Delpon paper recorder 26 times on GnomAD and mixed reviews. Needs review as no clear association. PMID:19122847. https://www.karger.com/Article/Abstract/113746. https://www.karger.com/Article/Abstract/113746
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
Unknown

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

Ellen McDonagh (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Due to new expert reviews and disputed evidence for this gene-disease causation, this gene has been demoted from Green to Red.
Created: 27 Feb 2019, 9:59 a.m.
This gene was given a validity classification of Disputed by the ClinGen validity curation group and is reflected by providing a Red review here.The gene-disease summary was downloaded on 20th Feb 2019.For the full report and publications see the ClinGen Gene Validity Curation for each gene here: https://search.clinicalgenome.org/kb/gene-validity/10152
Created: 20 Feb 2019, 2:47 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.

Mode of inheritance
Disputed

Phenotypes
Brugada syndrome; MONDO_0015263

James Eden (Manchester)

Red List (low evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 8 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: disputed association with Brugada syndrome 1 (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
?Brugada syndrome 6 (613119)

Publications

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

Caroline Wright (Genomics England Curator)

Comment when marking as ready: On Manchester diagnostic panel; Multiple unrelated patients in OMIM; Some functional evidence
Created: 11 Feb 2016, 11:18 a.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Variants detected in individuals with 2 different phenotypes - Brugada syndrome and periodic paralysis. Abbot et al report expression at low levels in the heart. 2 variants reported: T4A which we would consider unlikely / polymorphism (0.4 percentage of East Asians on gnomAD). R99H - which has conflicting interpretations on ClinVar (unlikely UV likely and pathogenic). Could be a potential candidate gene but zero evidence at present.
Created: 25 Jan 2019, 1:15 p.m.

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

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Red
  • South West GLH
  • London South GLH
  • North West GLH
  • Expert list
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • ?Brugada syndrome 6 (613119)
  • Brugada syndrome 6
OMIM
604433
Clinvar variants
Variants in KCNE3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Feb 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: kcne3 has been classified as Red List (Low 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 KCNE3. Mode of inheritance for gene KCNE3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to KCNE3.

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 KCNE3. Added phenotypes ?Brugada syndrome 6 (613119) for gene: KCNE3 Publications for gene KCNE3 were changed from to 19122847; 27761167 Rating Changed from Green List (high evidence) to Green List (high evidence)

11 Feb 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).

13 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE3 was added to Brugada syndromepanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE3 was added to Brugada syndromepanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE3 was added to Brugada syndromepanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene KCNE3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE3 was added to Brugada syndromepanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNE3 was added to Brugada syndromepanel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list