Brugada syndrome and cardiac sodium channel disease

Gene: KCNE3

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

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

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

• 19122847
• 27761167

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

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.

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