Brugada syndrome and cardiac sodium channel disease
Gene: SCN10AComment 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
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
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/10161Created: 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
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
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 panelCreated: 11 Feb 2016, 11:25 a.m.
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.
Phenotypes for gene: SCN10A were changed from Episodic pain syndrome, familial, 2 (615551) to Brugada syndrome, MONDO:0015263
Gene: scn10a has been classified as Red List (Low Evidence).
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
Source London South GLH was added to SCN10A.
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)
This gene has been classified as Green List (High Evidence).
Publications for SCN10A were set to http://www.ncbi.nlm.nih.gov/pubmed/24998131
Publications for SCN10A were set to 24998131
Publications for SCN10A were set to http://www.ncbi.nlm.nih.gov/pubmed/24998131
Mode of inheritance for SCN10A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Green List (High Evidence).
SCN10A was created by OxfordGenetics
SCN10A was added to Brugada syndromepanel. Sources: Oxford Medical Genetics Laboratory