Early onset or syndromic epilepsy

Gene: SETD1B

Green List (high evidence)

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 3:53 p.m. | Last Modified: 20 Oct 2020, 3:53 p.m.

Panel Version: 2.193

A recent publication (PMID: 32546566) reports four additional patients with de novo SETD1B variants: a splice-site variant c.5589+1G>A (p.?), nonsense variants c.2932C>T: p.(Gln978Ter) and c.3964C>T p.(Gln1322Ter), and a missense variant c.5833T>C p.(Phe1945Leu). All individuals demonstrate a shared phenotype, including global developmental delay (two individuals with moderate ID), speech impairment, and seizures.

Created: 30 Jul 2020, 12:12 p.m. | Last Modified: 30 Jul 2020, 12:12 p.m.

Panel Version: 2.129

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

Insufficient evidence, single case report PMID 29322246 where two de novo variants were identified in two patients with features that included epilepsy.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability, epilepsy

Publications

• 29322246

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for SETD1B associated intellectual disability, epilepsy and autism. At least 3 variants reported in at least 3 unrelated cases who displayed epilepsy (PMID29322246; 31440728 31685013). Strucutral variants have also been reported that encompass SETD1B (PMID 20648245; 27106595; 25428890; 22369279).

Created: 31 Mar 2020, 5:19 p.m. | Last Modified: 31 Mar 2020, 5:33 p.m.

Panel Version: 2.34

Comment on mode of inheritance: Mode of inheritance obtained from Gen2Phen

Created: 31 Mar 2020, 5:17 p.m. | Last Modified: 31 Mar 2020, 5:17 p.m.

Panel Version: 2.31

Comment when marking as ready: Based on reviewers' comments.

Created: 11 Dec 2018, 1:35 p.m.

Green List (high evidence)

Another individual with a de novo variant in this gene and epilepsy reported in 31440728 bringing the total to three, and possibly two more in 31685013.

Created: 25 Jan 2020, 4:12 a.m. | Last Modified: 25 Jan 2020, 4:12 a.m.

Panel Version: 2.0

Seizures are part of the phenotype; however, only two unrelated individuals described.

Created: 21 Aug 2018, 9:22 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy with myoclonic absences; intellectual disability

Publications

• 29322246
• 31440728
• 31685013

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