Inherited polyposis and early onset colorectal cancer - germline testing
Gene: MLH1EnsemblGeneIds (GRCh38): ENSG00000076242
EnsemblGeneIds (GRCh37): ENSG00000076242
OMIM: 120436, Gene2Phenotype
MLH1 is in 36 panels
7 reviews
Ivone Leong (Genomics England Curator)
As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.Created: 31 Jul 2019, 12:34 p.m. | Last Modified: 31 Jul 2019, 12:34 p.m.
Panel Version: 0.48
Rachel Robinson (Leeds Genetics Laboratory)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Lara Hawkes (Genomics England)
Clare Turnbull (Queen Mary University London)
Tumor Suppressor. Biallelic phenotype.Created: 5 Jul 2017, 12:19 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Lynch Syndrome; CMMRD
Sarah Leigh (Genomics England Curator)
Comment when marking as ready: Associated with phenotypes in OMIM and as a confirmed G2P associateions. At least 8 variants reported in Mismatch repair cancer syndrome 276300 and one in Muir-Torre syndrome 158320, however, these phenotypes do not include hamartomatous polyps characteristic of Peutz-Jeghers syndrome. No polyps are associated with colorectal cancer, hereditary nonpolyposis, type 2 609310Created: 11 Apr 2017, 3:01 p.m.
Comment on phenotypes: Also associated with Colorectal cancer, hereditary nonpolyposis, type 2 609310Created: 11 Apr 2017, 2:57 p.m.
Ellen Thomas (Genomics England Curator)
Comment on list classification: Current diagnostic.Created: 7 Feb 2016, 9:16 p.m.
Ian Frayling (Cardiff University)
http://chromium.lovd.nl/LOVD2/colon_cancer/home.php?select_db=MLH1
Biallelic mutations cause Constitutional Mismatch Repair Disorder (CMMR-D)Created: 8 Dec 2015, 2:21 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications
- Thompson BA, Spurdle AB, Plazzer J-P, Greenblatt M, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capella G, du Sart D, Fabre A, Farrell MP, Farrington S, Frayling IM, et al., on behalf of InSiGHT, Macrae F, Genuardi M. (2014) Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nature Genetics 46:107-115
- doi:10.1038/ng.2854.
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Green
- NHS GMS
- Expert List
- Phenotypes
-
- Colorectal cancer, hereditary nonpolyposis, type 2, OMIM:609310
- Mismatch repair cancer syndrome, OMIM:276300
- Muir-Torre syndrome, OMIM:158320
- OMIM
- 120436
- Clinvar variants
- Variants in MLH1
- Penetrance
- None
- Panels with this gene
-
- Inherited MMR deficiency (Lynch syndrome)
- Familial breast cancer
- Ovarian cancer pertinent cancer susceptibility
- Endometrial cancer pertinent cancer susceptibility
- Inherited prostate cancer
- Brain cancer pertinent cancer susceptibility
- Haematological malignancies cancer susceptibility
- Inherited pancreatic cancer
- Pigmentary skin disorders
- Genodermatoses with malignancies
- Familial rhabdomyosarcoma
- Haematological malignancies for rare disease
- Inherited polyposis and early onset colorectal cancer - germline testing
- Fetal anomalies
- Bladder cancer pertinent cancer susceptibility
- Childhood solid tumours cancer susceptibility
- Multiple monogenic benign skin tumours
- Familial Tumours Syndromes of the central & peripheral Nervous system
- Upper gastrointestinal cancer pertinent cancer susceptibility
- Sarcoma cancer susceptibility
- Inherited renal cancer
- Intellectual disability
- Prostate cancer pertinent cancer susceptibility
- Neurofibromatosis Type 1
- Colorectal cancer pertinent cancer susceptibility
- Adult solid tumours for rare disease
- Additional findings health related - CNV analysis adult specific
- Renal cancer pertinent cancer susceptibility
- GI tract tumours
- Sarcoma susceptibility
- Additional findings health related - adult specific
- Childhood solid tumours
- Adult solid tumours cancer susceptibility
- Endocrine neoplasia
- Inherited ovarian cancer (without breast cancer)
- Additional findings health related
History Filter Activity
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: MLH1 were changed from Colorectal cancer, hereditary nonpolyposis, type 2, OMIM:609310; Mismatch repair cancer syndrome, OMIM:276300; Muir-Torre syndrome OMIM:158320 to Colorectal cancer, hereditary nonpolyposis, type 2, OMIM:609310; Mismatch repair cancer syndrome, OMIM:276300; Muir-Torre syndrome, OMIM:158320
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: MLH1 were changed from Mismatch repair cancer syndrome 276300 AR; Gastrointestinal and Colorectal Cancer; High Risk Colorectal Cancer; Muir-Torre syndrome 158320 AD to Colorectal cancer, hereditary nonpolyposis, type 2, OMIM:609310; Mismatch repair cancer syndrome, OMIM:276300; Muir-Torre syndrome OMIM:158320
Set Phenotypes
Ivone Leong (Genomics England Curator)Added phenotypes Mismatch repair cancer syndrome 276300 AR; Gastrointestinal and Colorectal Cancer; High Risk Colorectal Cancer; Muir-Torre syndrome 158320 AD for gene: MLH1
Set mode of inheritance
Ivone Leong (Genomics England Curator)Mode of inheritance for gene: MLH1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Entity classified by Genomics England curator
Ivone Leong (Genomics England Curator)Gene: mlh1 has been classified as Green List (High Evidence).
Created, Added New Source, Set mode of inheritance
Ivone Leong (Genomics England Curator)gene: MLH1 was added gene: MLH1 was added to Inherited polyposis. Sources: Expert List,NHS GMS Mode of inheritance for gene: MLH1 was set to