MUTYH-associated Polypsis (MAP)

MUTYH-associated polyposis is a colorectal cancer predisposition syndrome typically characterized by tens to hundreds of adenomatous polyps in the gastrointestinal tract.


MUTYH-associated polyposis is a colorectal cancer predisposition syndrome typically characterized by tens to hundreds of adenomatous polyps in the gastrointestinal tract.

Disease Name 
MUTYH-associated polyposis (MAP)
Colorectal cancer
Disease Information 

Germline bi-allelic mutations in MUTYH (one mutation in each gene copy) cause MUTYH-associated polyposis (MAP) and account for >1% of all colorectal cancer (CRC) cases.1 While most hereditary cancer syndromes are inherited in an autosomal dominant pattern, MAP has autosomal recessive inheritance. ~1% of the Caucasian population has one MUTYH mutation and is a carrier of this syndrome.2

MUTYH encodes a protein that participates in the base-excision DNA repair pathway. Phenotypic expression is variable, but MAP often presents very similarly to familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP). However, it is possible for patients with MAP to develop CRC without polyposis, or to have serrated polyps or hyperplastic polyps in addition to adenomas. Sequence variants account for >99% of documented mutations, although large deletions have been reported.9,10

Two common missense mutations, p.Y179C and p.G396D (originally designated as Y165C and G382D), can either be homozygous or together in a compound heterozygote state in about 80% of Northern European patients with MAP; however, over 300 mutations have been described to date.11 

Individuals with MAP have been estimated to have a up to an 80% chance of developing CRC in their lifetimes.3 Individuals with MAP also have increased risks for colorectal polyposis, duodenal polyposis, and cancers of the duodenum, stomach, endometrium, and possibly breast.4-7 Additionally, while it remains an area of some debate, research has suggested that carriers of one of the two common founder mutations in MUTYH (p.G396D and p.Y179C) are at a roughly 2-fold increased risk of developing CRC.8

Testing Benefits & Indication 

Genetic testing of MUTYH can provide confirmation of a clinical diagnosis of  MAP. Once the causative mutations have been identified in someone, testing of at-risk family members can help identify carriers before clinical manifestations are present, in order to provide proper surveillance and medical care. 

MUTYH testing may be considered in patients with a personal or family history of any of the following:12-14

  • >10 colorectal adenomas
  • Colorectal cancer diagnosed before age 40
  • A family history of colorectal cancer consistent with autosomal recessive inheritance
  • >20 serrated polyps of any size distributed throughout the colon with some adenomas
  • Known MUTYH mutation(s) in the family

MUTYH testing can be done concurrently with APC testing (see Adenomatous Polyposis) or sequentially. Testing is also indicated in simplex patients with consanguineous parents, or in patients with a known MUTYH familial mutation.

Test Description 

MUTYH coding exons 1-16 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons 1-16.Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology, using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.15  Gross deletion/duplication analysis of MUTYH using read-depth from NGS data is also performed. Any copy number changes detected by NGS are confirmed by targeted chromosomal microarray and/or multiplex ligation-dependent probe amplification (MLPA).

Mutation Detection Rate 

MUTYH mutations are detected in 5-10% of patients with 10-999 adenomas (clinical sensitivity).12 Ambry’s MUTYH analysis is capable of detecting >99.9% of described mutations in the gene, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Turnaround Time 
4661 MUTYH Gene Sequence and Deletion/Duplication Analysis                                   14-21
4662 MUTYH  Specific Site Analysis 7-14
8726 Adenomatous Polyposis
(APC and MUTYH sequence and deletion/duplication analysis)


  1. Samadder NJ, et al. Hereditary and common familial colorectal cancer: evidence for colorectal screening. Digestive Diseases and Sciences. 2015. 60(3):734-47.
  2. Aretz S, et al. MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events. Eur J Hum Genet. 2014. 22(7):923-9.
  3. Jenkins MA, et al. Risk of colorectal cancer in monoallelic and biallelic carriers MYH mutations: a population-based case-family study. Cancer Epidemiol Biomarkers Prev. 2006. 15(2):312-314.
  4. Nielsen M, et al. Duodenal carcinoma in MUTYH‐associated polyposis. Journal of Clinical Pathology. 2006. 59(11):1212-5.
  5. Vogt S, et al. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterology. 2009. 137(6):1976-85.e10.
  6. Rennert G, et al. MutYH mutation carriers have increased breast cancer risk. Cancer. 2012. 118:1989-93.
  7. 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.e5.
  8. Win AK, et al. Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. Int J Cancer. 2011. 129(9): 2256-2262.
  9. Rouleau E, et al. First large rearrangement in the MUTYH gene and attenuated familial adenomatous polyposis syndrome. Clin Genet. 2011. 80(3):301-3.
  10. Torrezan GT, et al. Breakpoint characterization of a novel large intragenic deletion of MUTYH detected in a MAP patient: Case report. BMC Medical Genetics. 2011. 12:128.
  11. Out AA, et al. Leiden Open Variation Database of the MUTYH gene. Hum Mutat. 2010. 31(11):1205-15.
  12. Grover S, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA. 2012. 308(5):485-92.
  13. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015. 110(2):223-62.
  14. Hegde M, et al. ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genet Med. 2014. 16(1):101-16.
  15. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.