Long QT syndrome

Gene: SCN4B

Red List (low evidence)

SCN4B (sodium voltage-gated channel beta subunit 4)
EnsemblGeneIds (GRCh38): ENSG00000177098
EnsemblGeneIds (GRCh37): ENSG00000177098
OMIM: 608256, Gene2Phenotype
SCN4B is in 4 panels

7 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

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

Red List (low evidence)

Not enough evidence
Created: 18 Sep 2019, 9:20 p.m. | Last Modified: 18 Sep 2019, 9:20 p.m.
Panel Version: 1.38

Rebecca Whittington (South West GLH)

Red List (low evidence)

Atrial fibrillation, familial, 17 (OMIM 611819), Long QT syndrome-10 (OMIM 611819).
Created: 25 Mar 2019, 4:30 p.m.
Looks to be evidence in the Medeiros-Domingo paper (PMID 17592081) of a variant that tracked in a family, not on GnomAD and also functional evidence. PMID: 23631430. PMID: 23604097.
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

James Eden (Manchester)

Red List (low evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 9 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: no stated association with Long QT syndrome, disputed association with Brugada syndrome (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

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

Phenotypes
Long QT syndrome-10 (611819)

Publications

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

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

This appears to be a good functional candidate for LQT (gain of function) however very small number of case reports.
Created: 3 Mar 2016, 9:29 a.m.

Mode of pathogenicity
Other - please provide details in the comments

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

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.
Comment on mode of pathogenicity: Gain-of-function variants according to reviewer.
Created: 4 Mar 2016, 4:19 p.m.
Comment on list classification: Demoted from green to red due to reviewer's comments.
Created: 4 Mar 2016, 4:18 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 = 2.
Created: 19 Feb 2016, 11:05 a.m.

Bill Newman (Manchester Centre for Genomic Medicine)

Red List (low evidence)

I can only find a single report of a single case associated with this phenotype
Created: 2 Dec 2015, 3:39 p.m.

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • UKGTN
  • Expert list
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Long QT syndrome-10
  • Long QT syndrome-10 (611819)
OMIM
608256
Clinvar variants
Variants in SCN4B
Penetrance
Complete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

21 Feb 2019, Gel status: 1

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to SCN4B. Mode of inheritance for gene SCN4B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to SCN4B.

14 Feb 2019, Gel status: 1

Added New Source, Set Phenotypes, Set publications

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to SCN4B. Added phenotypes Long QT syndrome-10 (611819) for gene: SCN4B Publications for gene SCN4B were changed from PMID: 17592081 to 17592081

4 Mar 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

4 Mar 2016, Gel status: 1

Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

Mode of pathogenicity for SCN4B was changed to Other - please provide details in the comments

4 Mar 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SCN4B were set to PMID: 17592081

4 Mar 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

13 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN4B was added to Long QT syndromepanel. Sources: UKGTN

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SCN4B was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN4B was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,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 SCN4B was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN4B was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,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 SCN4B was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN4B was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN4B was added to Long QT syndromepanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list