Intellectual disability
Gene: TOR1A

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

5 reviews

Sarah Leigh (Genomics England Curator)

After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

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

Created: 28 Jan 2021, 5:48 p.m.
Last Modified: 28 Jan 2021, 5:48 p.m.
Panel version: 3.744

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

24896178

Created: 31 Oct 2017, 9:24 a.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.4

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

Created: 2 Aug 2017, 11:18 p.m.

Panel version: 1.354

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.

Created: 20 Jul 2017, 2:15 p.m.

Panel version: 1.241

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

NHS GMS
Expert Review Green

Phenotypes

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

OMIM

605204

Clinvar variants

Variants in TOR1A

Penetrance

Complete

Publications

Panels with this gene