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Intellectual disability

Gene: CLTC

Green List (high evidence)

CLTC (clathrin heavy chain)
EnsemblGeneIds (GRCh38): ENSG00000141367
EnsemblGeneIds (GRCh37): ENSG00000141367
OMIM: 118955, Gene2Phenotype
CLTC is in 4 panels

2 reviews

Helen Brittain (Genomics England Curator)

Comment when marking as ready: Sufficient cases, appropriate phenotype
Created: 5 Mar 2018, 11:33 a.m.

Louise Daugherty (Genomics England Curator)

Comment on list classification: Changed gene from status Amber to Green after internal review with clinical team. It was noted that it was helpful to see that the variants include truncations and are from several sources.
Created: 26 Feb 2018, 5:18 p.m.
This is a probable DD gene in Gene2Phenotype for Epilepsy and intellectual disability and a possible DD gene in Gene2Phenotype for Overgrowth intellectual disability
Created: 20 Feb 2018, 1:41 p.m.
Comment on list classification: Changed rating from Red to Amber. To be discussed with internal clinical team regarding whether this gene could be rated Green on the ID panel.
Created: 20 Feb 2018, 1:26 p.m.
Comment on publications: added publications to support the ID phenotype. More than three unrelated cases with autosomal dominant mental retardation-56 (MRD56). De Mari et al., 2016 (PMID:26822784) identified a de novo heterozygous frameshift mutation in the CLTC gene in a young patient, the authors postulated haploinsufficiency of CLTC as the pathogenetic mechanism. Hamdan et al., 2017 (PMID:29100083) identified de novo heterozygous missense mutations in the CLTC gene in 12 unrelated patients with MRD56 in several cohorts of patients with developmental delay and epilepsy. There were 5 truncating mutations, 2 small in-frame deletions, 1 splice site mutation, and 3 missense mutations, 1 of which was recurrent and found in 3 unrelated patients. Individuals with refractory epilepsy were found to carry variants in the first section of the clathrin light chain-binding domain, whereas truncating mutations affecting the C terminus tended to be associated with hypotonia, global developmental delay, and intellectual disability.
In both studies by De Mari et al. and Hamdan et al. functional studies of the variant and studies of patient cells were not performed.
Created: 20 Feb 2018, 1:13 p.m.
Comment on phenotypes: added phenotype from OMIM, orphanet and DDD project
Created: 20 Feb 2018, 12:58 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Mental retardation, autosomal dominant 56, 617854
  • Autosomal dominant non-syndromic intellectual disability, Epilepsy and intellectual disability
OMIM
118955
Clinvar variants
Variants in CLTC
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Mar 2018, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for CLTC were set to Mental retardation, autosomal dominant 56, 617854; Autosomal dominant non-syndromic intellectual disability, Epilepsy and intellectual disability

12 Mar 2018, Gel status: 4

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.

12 Mar 2018, Gel status: 4

Removed Source, Added New Source

Ellen McDonagh (Genomics England Curator)

Source Gene2Phenotype was removed from CLTC. Panel: Intellectual disability Other was added to CLTC. Panel: Intellectual disability

12 Mar 2018, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

CLTC was added to Intellectual disability panel. Sources: Gene2Phenotype,Expert Review Green

12 Mar 2018, Gel status: 4

Created

Ellen McDonagh (Genomics England Curator)

CLTC was created by Ellen McDonagh