Invitae MUTYH-Associated Polyposis Syndrome Test


Test description

This test analyzes the MUTYH gene. Individuals who have pathogenic variants in both copies of this gene can develop MUTYH-associated polyposis syndrome (MAP), a colorectal cancer predisposition syndrome.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)


Alternative tests to consider

MUTYH can also be ordered as part of a broader panel to test for different types of hereditary cancer, including colorectal cancer. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.

MUTYH-associated polyposis syndrome (MAP)

MUTYH-associated polyposis (MAP) is a colorectal cancer predisposition syndrome characterized by the growth of tens to hundreds of adenomatous colorectal polyps. MAP generally has a less severe clinical presentation than familial adenomatous polyposis (FAP), a clinically similar condition in which hundreds to thousands of colorectal polyps develop. Individuals with MAP have a 43%-100% lifetime risk of developing colorectal cancer. Occasionally, individuals with MAP will develop colorectal cancer in the absence of polyposis. MAP is also associated with an increased risk of developing upper gastrointestinal tract cancers, including duodenal adenomas. Extra-gastrointestinal manifestations include jaw-bone cysts and congenital hypertrophy of the retinal pigment epithelium (CHRPE).

Individuals with pathogenic variants in both copies of MUTYH have an increased risk of malignancy compared to the average person, but not everyone with these variants will actually develop cancer. Further, MAP can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.

Cancer typeLifetime risk
Colorectal 43%-100%
Duodenal 4%

The MUTYH gene is the only gene known to be associated with MAP. Pathogenic variants are identified in greater than 99% of affected individuals. Sequence analysis of MUTYH detects approximately 99% of pathogenic variants. The proportion of MAP cases caused by deletions or duplications within the MUTYH gene is unknown but appears to be small.

MAP is inherited in an autosomal recessive pattern. There is some evidence to suggest that individuals who carry a single pathogenic variant may be at increased risk for colorectal cancer.

Approximately 1%-2% of individuals of northern European ancestry are carriers of a MUTYH variant. The prevalence of MAP in this population is estimated at 1 in 20,000 to 1 in 40,000. It is difficult to determine the prevalence of this condition in other ethnicities because the carrier frequency can vary significantly.

Clinical testing for MAP should be considered in individuals with the following:

  • one to ten colorectal adenomas before age 40
  • between ten and a few hundred colorectal adenomas and/or hyperplastic polyps
  • more than 100 polyps in the absence of a germline APC pathogenic variant
  • colorectal cancer with the somatic KRAS mutation c.34G>T in codon 12
  • a family history of colon cancer (with or without polyps) that is consistent with autosomal recessive inheritance

Criteria for evaluating a family for MAP have been established by the National Comprehensive Cancer Network:

  1. Brand, R, et al. MUTYH-Associated Polyposis. 2012 Oct 04. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 23035301
  2. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  3. Lubbe, SJ, et al. Clinical implications of the colorectal cancer risk associated with MUTYH mutation. J. Clin. Oncol. 2009; 27(24):3975-80. doi: 10.1200/JCO.2008.21.6853. PMID: 19620482
  4. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. Accessed September 2015.
  5. National Library of Medicine, Genetics Home Reference: MUTYH. Accessed June 2015.
  6. Rennert, G, et al. MutYH mutation carriers have increased breast cancer risk. Cancer. 2012; 118(8):1989-93. doi: 10.1002/cncr.26506. PMID: 21952991
  7. Vogt, S, et al. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterology. 2009; 137(6):1976-85.e1-10. doi: 10.1053/j.gastro.2009.08.052. PMID: 19732775
  8. Wasielewski, M, et al. Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer. Breast Cancer Res. Treat. 2010; 124(3):635-41. doi: 10.1007/s10549-010-0801-7. PMID: 20191381

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
MUTYH NM_001128425.1