Brugada syndrome

Gene: SCN10A

Red List (low evidence)

SCN10A (sodium voltage-gated channel alpha subunit 10)
EnsemblGeneIds (GRCh38): ENSG00000185313
EnsemblGeneIds (GRCh37): ENSG00000185313
OMIM: 604427, Gene2Phenotype
SCN10A is in 6 panels

6 reviews

Ivone Leong (Genomics England Curator)

Comment on phenotypes: This gene is also associated with Episodic pain syndrome, familial, 2 (615551)
Created: 2 Mar 2021, 11:58 a.m. | Last Modified: 2 Mar 2021, 11:58 a.m.
Panel Version: 2.22

Rebecca Whittington (South West GLH)

Green List (high evidence)

Episodic pain syndrome, familial, 2 (OMIM 615551), PR Interval, variation in (OMIM %108980)
Created: 25 Mar 2019, 4:30 p.m.
Rare. Evidence for association SNP / polygenic contribution Largest study in Hu paper PMID:24998131. PMID:25691538. PMID:25691686. PMID:25053638. https://www.ncbi.nlm.nih.gov/pubmed/28407228?dopt=Abstract.
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, 10 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/10161
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 1; MONDO_0011001

James Eden (Manchester)

Red List (low evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 85 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: 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
Episodic pain syndrome, familial, 2 (615551)

Publications

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

Caroline Wright (Genomics England Curator)

Comment when marking as ready: 2014 paper: Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome.
Created: 11 Feb 2016, 11:27 a.m.
Comment on list classification: On Manchester diagnostic panel
Created: 11 Feb 2016, 11:25 a.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

On ClinVar just 1 variant in this gene is classified as pathogenic however it was detected in someone with episodic pain syndrome (not BS). All variants detected in Brugada syndrome (>100) classed as UV suggesting there is an absence of fundamental evidence that variants in this gene cause BS. Many of the variants detected in early reports of in this gene were later noted to have relatively high frequencies in populations therefore caution should be applied to previous case reports e.g. Hu et al 2014.
Created: 25 Jan 2019, 1:15 p.m.
Hu et al 2014 reported detecting variants in SCN10A in 16.7% of BrS probands. However this figure has not been replicated in other multicentre-cohorts (Behr et al 2015). Most of the variants reported by Hu et al represent rare variants <1% on ExAC however some are present in ExAC at frequencies of up to 15%. Therefore, most of these variants would not be classified as pathogenic according to current UK best practice.
Created: 3 Mar 2016, 10:24 a.m.

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Red
  • South West GLH
  • London South GLH
  • North West GLH
Phenotypes
  • Brugada syndrome, MONDO:0015263
OMIM
604427
Clinvar variants
Variants in SCN10A
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Mar 2021, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SCN10A were changed from Episodic pain syndrome, familial, 2 (615551) to Brugada syndrome, MONDO:0015263

27 Feb 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: scn10a 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 SCN10A. Mode of inheritance for gene SCN10A 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 SCN10A.

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 SCN10A. Added phenotypes Episodic pain syndrome, familial, 2 (615551) for gene: SCN10A Publications for gene SCN10A were changed from http://www.ncbi.nlm.nih.gov/pubmed/24998131 to 24998131; 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).

11 Feb 2016, Gel status: 4

Set publications

Caroline Wright (Genomics England Curator)

Publications for SCN10A were set to http://www.ncbi.nlm.nih.gov/pubmed/24998131

11 Feb 2016, Gel status: 4

Set publications

Caroline Wright (Genomics England Curator)

Publications for SCN10A were set to 24998131

11 Feb 2016, Gel status: 4

Set publications

Caroline Wright (Genomics England Curator)

Publications for SCN10A were set to http://www.ncbi.nlm.nih.gov/pubmed/24998131

11 Feb 2016, Gel status: 4

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

Mode of inheritance for SCN10A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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).

6 Jan 2016, Gel status: 0

Created

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

SCN10A was created by OxfordGenetics

6 Jan 2016, Gel status: 0

Added New Source

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

SCN10A was added to Brugada syndromepanel. Sources: Oxford Medical Genetics Laboratory