• Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit




Associated disorders

The MUTYH gene is associated with autosomal recessive MUTYH-associated polyposis (MAP) (MedGen UID: 332993).

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MUTYH is a tumor suppressor gene that is important for repairing DNA damage. The MUTYH gene encodes a DNA glycosylase involved in oxidative DNA damage repair. Loss of MUTYH function due to mutations causes defective DNA repair, leading to accumulation of errors in the DNA sequence as cells continue to divide, thereby increasing the risk of tumor formation.

MedGen UID: 332993

Clinical condition
MUTYH-associated polyposis (MAP) is an adult-onset colorectal cancer predisposition syndrome characterized by the growth of tens to hundreds of adenomatous colorectal polyps (PMID: 23035301, 19620482). Features typically present at approximately 47 years of age (PMID: 19506731). Polyp types can include conventional adenomas, as well as serrated adenomas, hyperplastic polyps, and mixed (hyperplastic and adenomatous) polyps (PMID: 18564191). 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 (PMID: 20301519, (external) 20301519”:http://www.ncbi.nlm.nih.gov/pubmed/20301519). Individuals with MAP have a 43–100% lifetime risk of developing colorectal cancer (PMID: 23035301, 19620482:”(external) National Library of Medicine. Genetics Home Reference: MUTYH gene. Accessed February 2018”:http://ghr.nlm.nih.gov/gene/MUTYH). Occasionally, colon cancer may develop in the absence of polyposis polyps (PMID: 19245865, 15931596, 19032956).

MAP is also associated with an approximately 4% risk of developing upper gastrointestinal tract cancers including duodenal malignancy secondary to duodenal adenomas, found in 17–25% of affected individuals (PMID: 23035301). Extra-gastrointestinal manifestations are uncommon, but may include jaw-bone cysts and congenital hypertrophy of the retinal pigment epithelium (CHRPE) (PMID: 19732775). It has also been suggested that there is an increased risk of other extraintestinal malignancies such as ovarian, bladder, endometrial, skin, and thyroid cancers (PMID: 19732775, 17956577, 23035301).

MAP occurs in individuals with two pathogenic variants in MUTYH—one in each copy of their MUTYH genes. Individuals with a single MUTYH pathogenic variant are not affected with MAP. Several studies have indicated that the presence of a single pathogenic variant may modify lifetime cancer risks. The risk for colon cancer is not well defined, but large population studies have demonstrated that the risk is modestly increased over the general population (PMID: 19394335). Other studies suggest that the risk for colorectal cancer may be two-to-three times that of the general population (PMID: 19245865, 16492921, 24444654).

There is also evidence suggesting an association between MUTYH and breast cancer in individuals with a single pathogenic variant (PMID: 19732775, 21171015, 21952991, 27194394). Therefore, MUTYH is available as a “preliminary-evidence” gene on the Invitae Breast Cancer Panel and the Invitae Breast and Gyn Cancers Panel. Preliminary-evidence genes are selected from an extensive review of the literature and expert recommendations, but the association between the gene and the specific condition has not been completely established. This uncertainty may be resolved as new information becomes available, and therefore clinicians may continue to order these preliminary-evidence genes.

Gene information
MUTYH, formerly known as MYH, is a tumor-suppressor gene that is important for repairing DNA damage. The MUTYH gene encodes a DNA glycosylase involved in oxidative DNA damage repair. Loss of MUTYH function causes defective DNA repair, which leads to an accumulation of errors in the DNA sequence as cells continue to divide, thereby increasing the risk of tumor formation (NCBI Gene. Gene ID:4595 Accessed February 2017).

MAP has autosomal recessive inheritance. Affected individuals have two pathogenic variants—one in each copy of their MUTYH genes. Affected individuals will pass one pathogenic MUTYH variant to all of their children.

Individuals with a single pathogenic variant in the MUTYH gene are considered carriers of MAP. If only one parent is an unaffected carrier, he or she has a 50% risk of passing the pathogenic variant on to each child. If both parents are unaffected carriers, each of their children has a 1 in 4, or 25%, chance of having MAP.

In the Northern European population, 1.5–2% of individuals are carriers of one of two well-described founder variants, c.536A>G (p.Tyr179Cys) in exon 7 and c.1187G>A (p.Gly396Asp) in exon 13 (PMID: 11818965, 12393807, 19245865). Up to 90% of individuals with MAP have one or both of these variants (PMID: 19245865).

Individuals with MAP are best served by seeking care through a clinic with experience treating this condition. Surveillance guidelines for individuals with MAP, as published by the National Comprehensive Cancer Network® (NCCN®), include the following (NCCN. Genetic/Familial High Risk Assessment: Colorectal. Version 3.2017, accessed February 2018.).

  • Annual physical examination
  • Begin colonoscopies between 25-30 years of age and if negative, repeat every 2-3 years thereafter
  • Consider upper endoscopy (including complete visualization of the ampulla of Vater) beginning at 30-35 years of age; if negative, repeat every 4 years

For affected individuals with polyps:

  • For those under 21 years of age with fewer than 20 adenomas all less than 1 cm in size, and absence of advanced pathology:
    • Colonoscopy and polypectomy every 1-2 years
    • Surgical evaluation and counseling, if appropriate
  • For those 21 years of age or older with fewer than 20 adenomas all less than 1 cm in size, and absence of advanced pathology:
    • Colonoscopy and polypectomy every 1-2 years
    • Colectomy with ileorectal anastomosis (IRA) may be considered
    • Surgical evaluation and counseling, if appropriate
  • For those with significant polyposis not manageable with polypectomy:
    • Colectomy with ileorectal anastomosis (IRA)
    • Consider proctocolectomy with ileal pouch–anal anastomosis (IPAA) if dense rectal polyposis not manageable with polypectomy
    • If patient had colectomy with IRA, then endoscopic evaluation of rectum every 6-12 months, depending on polyp burden
      The use of chemoprevention can facilitate management of the remaining rectum post-surgery, although there are currently no FDA-approved medications for this indication.

Management for individuals with a single MUTYH pathogenic variant
Medical management and surveillance protocols for individuals with a single pathogenic variant in MUTYH have been developed by the NCCN® (NCCN. Genetic/Familial High Risk Assessment: Colorectal. Version 3.2017, accessed February 2018.).


  • Colonoscopy screening is recommended every 5 years beginning at age 40. If individual has first-degree relative with colorectal cancer, screening should begin 10 years prior to relative’s age at diagnosis if before 40.
  • If an individual is unaffected by colon cancer and has no family history of colon cancer, data are uncertain regarding whether specialized screening is warranted.
    AFFECTED: Individuals with colon/rectal cancer should follow surveillance recommendations post resection

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.

Knowing if pathogenic variants in MUTYH are present is advantageous. At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Furthermore, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant data regarding MUTYH are likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to diligently follow recommended screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.

Additional reference
Referenced with permission from the NCCN Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed February 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.

The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Review date: February 2018

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. In addition, the analysis covers the select non-coding variants specifically defined in the table below. 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