Arthrogryposis
Gene: METEnsemblGeneIds (GRCh38): ENSG00000105976
EnsemblGeneIds (GRCh37): ENSG00000105976
OMIM: 164860, Gene2Phenotype
MET is in 10 panels
3 reviews
Arina Puzriakova (Genomics England Curator)
The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.Created: 24 Feb 2025, 5:04 p.m. | Last Modified: 24 Feb 2025, 5:04 p.m.
Panel Version: 8.6
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: As reviewed by Dmitrijs Rots, two unrelated cases and functional evidence are available in support of the disease association. Hence, this gene can be promoted to green rating in the next GMS update.Created: 7 Nov 2024, 10:48 a.m. | Last Modified: 7 Nov 2024, 10:48 a.m.
Panel Version: 8.4
PMID:30777867 reported a four-generation arthrogryposis pedigree characterized by camptodactyly, limited forearm supination, and loss of myofibers in the forearms and hands. c.3701A>G (p.Tyr1234Cys) variant in MET gene segregated in heterozygous state in 11 affected family members in this family and was absent from 12 unaffected family members. Functional studies confirmed p.Y1234C variant caused the failure of activation of MET tyrosine kinase. A Met p.Y1232C mutant mouse model was established and the homozygous mice displayed embryonic lethality and complete loss of muscles that originated from migratory precursors. Heterozygous mice were born alive and showed reduction of the number of myofibers in both appendicular and axial muscles.
PMID:38429387 reported a second two-generation family with distal arthrogryposis and a MET variant (c.3704 A > G (p.Tyr1235Cys)), that was present in heterozygous state in both the mother and son.
This gene has been associated with arthrogryposis in OMIM (MIM #620019).Created: 7 Nov 2024, 10:46 a.m. | Last Modified: 7 Nov 2024, 10:46 a.m.
Panel Version: 8.1
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Arthrogryposis, distal, type 11, OMIM:620019
Publications
Dmitrijs Rots (Children's Clinical University Hospital)
Reported a second family case in PMID: 38429387 after PMID: 30777867 with functional evidence in 30777867.
Sources: LiteratureCreated: 21 Oct 2024, 12:37 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Arthrogryposis
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- NHS GMS
- Phenotypes
-
- ?Arthrogryposis, distal, type 11, OMIM:620019
- OMIM
- 164860
- Clinvar variants
- Variants in MET
- Penetrance
- unknown
- Publications
- Mode of Pathogenicity
- Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
- Panels with this gene
History Filter Activity
Removed Tag
Arina Puzriakova (Genomics England Curator)Tag Q3_24_promote_green was removed from gene: MET.
Added New Source, Added New Source, Status Update
Arina Puzriakova (Genomics England Curator)Source NHS GMS was added to MET. Source Expert Review Green was added to MET. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: met has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: MET were changed from Arthrogryposis to ?Arthrogryposis, distal, type 11, OMIM:620019
Set publications
Achchuthan Shanmugasundram (Genomics England Curator)Publications for gene: MET were set to PMID: 38429387; 30777867
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_24_promote_green tag was added to gene: MET.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance, Set mode of pathogenicity
Dmitrijs Rots (Children's Clinical University Hospital)gene: MET was added gene: MET was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: MET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MET were set to PMID: 38429387; 30777867 Phenotypes for gene: MET were set to Arthrogryposis Penetrance for gene: MET were set to unknown Mode of pathogenicity for gene: MET was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: MET was set to GREEN