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Intellectual disability

Gene: TOR1A

Amber List (moderate evidence)

TOR1A (torsin family 1 member A)
EnsemblGeneIds (GRCh38): ENSG00000136827
EnsemblGeneIds (GRCh37): ENSG00000136827
OMIM: 605204, Gene2Phenotype
TOR1A is in 10 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Upgraded from Red to Amber, but there is sufficient evidence linking biallelic variants to a relevant phenotype to rate this gene Green at the next GMS panel update (added 'for-review' tag)
Created: 28 Jan 2021, 5:50 p.m. | Last Modified: 28 Jan 2021, 5:50 p.m.
Panel Version: 3.745
Biallelic variants are associated with severe arthrogryposis and global developmental delay, including moderate to severe ID. At least 5 unrelated families have been reported with this phenotype (PMIDs: 30244176; 29053766; 28516161) which reaches threshold for inclusion on this panel.

On the other hand, monoallelic variants are associated with a phenotype primarily characterised by dystonia. There have been some reports of developmental delay, but cognitive function is mostly preserved. As highlighted in the previous review by Rebecca Foulger (Genomics England), the evidence linking monoallelic variants with ID is insufficient.
Created: 28 Jan 2021, 5:48 p.m. | Last Modified: 28 Jan 2021, 5:48 p.m.
Panel Version: 3.744

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218

Publications

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

TOR1A is listed as a known ID in Gilissen 2014 paper (PMID:24896178, Supplementary Table 10). However on searching for the source of the ID patients harbouring TOR1A variants, none were listed in PMID:23033978 (De Ligt et al. 2012) which was used to form part of the Gilissen ID list. No further ID evidence from the literature, and Helen Brittain confirms that the majority of the information aligns with causation for dystonia, rather than ID.
Created: 31 Oct 2017, 9:24 a.m.

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_gilissen_2014_known;in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : NA
Created: 27 Jul 2017, 8:45 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : gilissen_2014_known; manju_list; UKGTN_v12; neuro_20160418_strict; NA. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:34 p.m.

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

Publications

  • 24896178
  • Personal communication with NIHRBRRD BRIDGE SPEED
  • Version 12 ukgtn.nhs.uk

Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.
Created: 20 Jul 2017, 2:15 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Arthrogryposis multiplex congenita 5, OMIM:618947
  • Arthrogryposis multiplex congenita 5, MONDO:0100218
Tags
for-review
OMIM
605204
Clinvar variants
Variants in TOR1A
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: tor1a has been classified as Amber List (Moderate Evidence).

28 Jan 2021, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: TOR1A.

28 Jan 2021, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: TOR1A were set to 24896178

28 Jan 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, 128100; Dystonia, early-onset atypical, with myoclonic features; {Dystonia-1, modifier of} to Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218

28 Jan 2021, Gel status: 1

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: TOR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 1

Added New Source, Set publications

Ellen McDonagh (Genomics England Curator)

Expert Review Red was added to TOR1A. Panel: Intellectual disability Publications for gene TOR1A was set to ['24896178']

20 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

19 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

TOR1A was created by BRIDGE

19 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

TOR1A was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene