Test Catalog

Test ID: MYHZ    
MUTYH Gene, Full Gene Analysis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirmation of suspected clinical diagnosis of MUTYH-associated polyposis (MAP) in patients with adenomatous polyps or early-onset colorectal cancer


Identification of familial MUTYH mutations to allow for predictive or diagnostic testing in family members

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing to evaluate for mutations in the coding region of the MUTYH gene. Sanger sequencing may also be performed to confirm any detected variants.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Biallelic germline mutations in the MUTYH gene (also known as MYH) cause MUTYH-associated polyposis (MAP) syndrome, an autosomal recessive form of hereditary colorectal cancer. MAP is a polyposis syndrome typically associated with 10 to 100 adenomatous colon polyps, which in turn confer a significantly increased risk for colorectal cancer. Therefore, phenotypic overlap exists between MAP and attenuated familial adenomatous polyposis (FAP). However, the number of cumulative polyps is variable and can mimic both classic FAP, associated with hundreds to thousands of polyps, and Lynch syndrome, which is generally associated with very few (1-5) adenomatous polyps. Therefore, evaluation for MUTYH should be considered in patients with early onset colorectal cancer in whom a DNA mismatch repair (MMR) defect has not been identified.


Patients with biallelic MUTYH mutations are at risk for extracolonic manifestations including upper gastrointestinal polyps or cancer as well as other tumors. Congenital hyperpigmentation of the retinal epithelium (CHRPE), dental anomalies, dermal cysts, desmoid tumors, and osteomas may also occur, but to a lesser extent than what is observed in patients with FAP.


Literature suggests that monoallelic carriers may also be at increased risk for colon, gastric, breast, and endometrial cancer. Approximately 1% to 2% of mixed European Caucasian individuals are predicted to carry a MUTYH mutation. Therefore, the reproductive partners of monoallelic and biallelic carriers should be offered carrier screening to adequately assess the risk of their offspring to have MAP.


Two mutations, G396D and Y179C (originally known as G382D and Y165C), account for approximately 85% of the disease-causing MUTYH mutations in affected mixed European Caucasian individuals.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Some individuals who have a diagnosis of MUTYH-associated polyposis (MAP) or involvement of MUTYH may have a mutation that is not identified by this method (eg, promoter mutations, deep intronic mutations). The absence of a mutation, therefore, does not eliminate the possibility of a diagnosis of MUTYH-associated polyposis. For predictive testing of asymptomatic individuals, it is important to first document the presence of MUTYH gene mutations in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified. Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete. We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Technical Limitations:

Due to the limitations of next-generation sequencing, we can detect more than 93% of insertions and deletions up to 20 bases and 43 bases, respectively. If a diagnosis is still suspected, consider full gene sequencing using traditional Sanger methods. If results obtained do not match the clinical findings, additional testing should be considered.


Evaluation Tools:

Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently not validated.


Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.


Reclassification of Variants-Policy:

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. At this time, it is not standard practice for the laboratory to systematically re-review likely deleterious alterations or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008;10(4):294-300

2. Goodenberger M, Lindor NM: Lynch syndrome and MYH-associated polyposis: review and testing strategy. J Clin Gastroenterol 2011;45(6):488-500

3. Lindor NM, McMaster ML, Lindor CJ, et al: Concise handbook of familial cancer susceptibility syndromes. Second edition. J Natl Cancer Inst Monogr 2008;(38):1-93

4. Win AK, Cleary SP, Dowty JG, et al: Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. Int J Cancer 2011;129(9):2256-2262

5. MUTYH-Associated Polyposis-GeneReviews-NCBI Bookshelf. Available at  www.ncbi.nlm.nih.gov/books/NBK107219/

Special Instructions Library of PDFs including pertinent information and forms related to the test