• Test code: 01710
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

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. There is evidence to suggest individuals with a pathogenic variant in one copy of MUTYH (heterozygotes) have an increased risk for colorectal cancer.

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 an 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 (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 (PMID: 23035301). Occasionally, affected individuals 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 have also been reported.

While individuals with a pathogenic variant in one copy of MUTYH (heterozygotes) are not affected with MAP, there is evidence to suggest they have an increased risk of colorectal cancer. Specific cancer risks, however, are not well-established.

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 the clinical course, additional medical management strategies focused on cancer prevention and early detection may be beneficial. See the table below for MAP-associated cancer risks:

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

The MUTYH gene is the only gene known to be associated with MAP. 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:

  • 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: http://www.ncbi.nlm.nih.gov/books/NBK107219/ PMID: 23035301
  2. 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
  3. 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
  4. Barnetson, RA, et al. Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer. Clin. Genet. 2007; 72(6):551-5. doi: 10.1111/j.1399-0004.2007.00900.x. PMID: 17956577
  5. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed September 2019.
  6. National Library of Medicine, Genetics Home Reference: MUTYH. http://ghr.nlm.nih.gov/gene/MUTYH Accessed February 2018.
  7. Cleary, SP, et al. Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study. Gastroenterology. 2009; 136(4):1251-60. PMID: 19245865
  8. Jones, N, et al. Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH. Gastroenterology. 2009; 137(2):489-94, 494.e1; quiz 725-6. PMID: 19394335
  9. Win, AK, et al. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology. 2014; 146(5):1208-11.e1-5. PMID: 24444654
  10. Jenkins, MA, et al. Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol. Biomarkers Prev. 2006; 15(2):312-4. PMID: 16492921
  11. Win, AK, et al. Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. Int. J. Cancer. 2011; 129(9):2256-62. doi: 10.1002/ijc.25870. PMID: 21171015
  12. 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
  13. 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
  14. 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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

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