Adult solid tumours cancer susceptibility

Gene: MUTYH

Red List (low evidence)

Comment on list classification: The gene-disease association between MUTYH and hereditary cancers has been disputed by the ClinGen Hereditary Cancer GCEP - classified as Disputed for familial ovarian cancer (AR & AD), Disputed for AR hereditary breast carcinoma and Refuted for AD hereditary breast carcinoma, and Disputed for colorectal cancer. MUTYH is linked to familial adenomatous polyposis 2 and classified as Definitive in ClinGen. More information: https://search.clinicalgenome.org/kb/genes/HGNC:7527
Based on the available evidence, MUTYH should be demoted to Red for Adult solid tumours cancer susceptibility at the next GMS panel update.

Created: 29 Oct 2025, 5:27 p.m. | Last Modified: 29 Oct 2025, 5:27 p.m.

Panel Version: 2.34

For AD colorectal cancer, some studies suggested a slightly increased risk for colorectal cancer in monoallelic MUTYH variant carriers compared to controls (PMID: 21063410, 24444654, 23946381) and other studies suggested no increased risk for colorectal cancer in monoallelic MUTYH variant carriers (29478780, 33309985).

AR hereditary breast carcinoma and MUTYH relationship has been studied in only one large case-control study (PMID: 35172496). This study screened breast cancer cases from commercial laboratories and did NOT find significant association of biallelic variants in MUTYH with breast cancer.

A large case-control study [BCAC, with more than 48 thousand cases and controls (PMID: 33471991)] did not identify a significant association of aggregate loss of function (LOF) variants in MUTYH and AD breast cancer.

Case-control studies show inconclusive results or no increased risk for ovarian cancer in monoallelic and biallelic MUTYH variant carriers (PMIDs:19732775;27194394;27194394;35172496).

MUTYH is associated with Gastric cancer, somatic, 613659 (no MOI provided) and AR Adenomas, multiple colorectal, 608456 in OMIM (accessed 29th Oct 2025).

Created: 29 Oct 2025, 5:27 p.m. | Last Modified: 29 Oct 2025, 5:27 p.m.

Panel Version: 2.34

Phenotypes
Gastric cancer, somatic, OMIM:613659; Adenomas, multiple colorectal, OMIM:608456

Publications

• 21063410
• 24444654
• 23946381
• 29478780
• 33309985
• 33471991
• 35172496

Green List (high evidence)

As discussed at the Genomics Cancer Panel Workshop, 16th July 2019: the group agreed that there is enough evidence to rate this gene green

Created: 2 Aug 2019, 12:34 p.m. | Last Modified: 2 Aug 2019, 12:34 p.m.

Panel Version: 1.5

Green List (high evidence)

Tumor Suppressor.

Created: 5 Jul 2017, 12:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Colorectal cancer