• Test code: 01709
  • 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

Invitae Hereditary Polyposis Panel

Test description

The Invitae Hereditary Polyposis Panel analyzes the APC and MUTYH genes, which are associated with familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). These conditions are associated with an increased risk of developing adenomatous polyps and 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.

Order test

Primary panel (2 genes)

Alternative tests to consider

These genes can also be ordered individually or as part of broader multi-gene panels. Depending on the individual’s clinical and family history, a broader panel may be appropriate. Any of these broader panels can be ordered at no additional charge.


  • Familial adenomatous polyposis (FAP)
  • MUTYH-associated polyposis (MAP)

Clinical Subtypes:

  • Gardner syndrome
  • Attenuated familial adenomatous polyposis
  • APC-associated polyposis conditions

Colorectal cancer (CRC) is the third-most-common cancer diagnosis in the United States. Most cases are sporadic and not inherited; however, approximately 5%-10% of colorectal cancer is hereditary and due to an identifiable pathogenic variant.

Hereditary colorectal cancer syndromes that are covered by this test include familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), and MUTYH-associated polyposis (MAP). These disorders are associated with an increased lifetime risk of developing colorectal cancer.

Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of hundreds to thousands of precancerous (adenomatous) polyps, typically beginning in adolescence or early adulthood. Without a prophylactic colectomy, there can be up to a 100% lifetime risk of developing colon cancer.

Several clinical subtypes of FAP have been described. Gardner syndrome has the same disease progression and risk of colon cancer as classic FAP, but is also associated with the development of other extracolonic findings, both benign and malignant. These include desmoid tumors, sebaceous cysts, osteomas, supernumerary teeth, liver (hepatoblastomas) and central nervous system tumors (medulloblastomas), and cancers of the duodenum, exocrine pancreas, and thyroid (papillary adenocarcinoma). Turcot syndrome is a subtype of FAP that is characterized by numerous colon adenomas and medulloblastoma. Another subtype, attenuated familial adenomatous polyposis (AFAP), has a later age of onset and presents with fewer adenomatous polyps (<100). AFAP has an overall lower lifetime risk of developing colorectal cancer—approximately 70%.

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 FAP. Individuals with MAP have a 43%-100% lifetime risk of developing colorectal cancer. Occasionally, affected individuals will develop colon cancer in the absence of polyposis. MAP is also associated with an increased risk of developing upper gastrointestinal tract cancers, including duodenal adenomas and possibly other cancers.

Individuals affected with MAP have two pathogenic variants, one in each copy of their MUTYH genes. There is some evidence to suggest that individuals who have a single pathogenic variant in MUTYH may also be at slightly increased risk for colorectal cancer.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develoip cancer. Further, the same variant 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. For gene-associated cancer risks, see the tables below.

APC-Associated Conditions

Cancer typeCancer risk
ColonUp to 100% (70% for attenuated FAP)
SarcomaUp to 25%
Hepatoblastoma (up to age 5)1%-2%
GastricUp to 0.5%

MUTYH-Associated Polyposis

Cancer typeLifetime cancer risk

FAP has autosomal dominant inheritance. Most cases of FAP are inherited; however, up to 25% of cases are due to a spontaneous de novo mutation.

MAP is autosomal recessive, though some literature suggests that individuals who carry a single pathogenic variant may have an increased risk for colorectal cancer.

Colorectal cancer occurs in approximately 1 in 22 individuals in the general population.

APC-associated polyposis conditions historically accounted for approximately 0.5% of all colon cancer, but this number is decreasing with greater awareness, early detection, and intervention. Collectively, the APC-associated polyposis conditions have a prevalence of approximately 2-3 in 100,000 individuals.

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.

The Invitae Hereditary Polyposis Panel may be considered for individuals with a personal and/or family history of:

  • 10 or more colorectal adenomas and/or hyperplastic polyps
  • at least one colorectal adenoma before age 40
  • colorectal cancer before age 60
  • more than one primary colorectal cancer
  • multiple primary cancers associated with FAP, or MAP
  • close relatives with any of the above features

  1. American Society of Clinical Oncology, Cancer.Net: Familial Adenomatous Polyposis. http://www.cancer.net/cancer-types/familial-adenomatous-polyposis Accessed November 2017.
  2. Bianchi, LK, et al. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(2):180-5. doi: 10.1016/j.cgh.2007.11.018. PMID: 18237868
  3. Biasco, G, et al. Risk of duodenal cancer in patients with familial adenomatous polyposis. Gut. 2004; 53(10):1547; author reply 1547. doi: 10.1136/gut.2003.027771. http://ncbi.nlm.nih.gov/pubmed/15361514 PMID: 15361514
  4. 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
  5. Giardiello, FM, et al. Hepatoblastoma and APC gene mutation in familial adenomatous polyposis. Gut. 1996; 39(6):867-9. doi: 10.1136/gut.39.6.867. http://ncbi.nlm.nih.gov/pubmed/9038672 PMID: 9038672
  6. Giardiello, FM, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993; 34(10):1394-6. doi: 10.1136/gut.34.10.1394. PMID: 8244108
  7. Giardiello, FM, et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N. Engl. J. Med. 1997; 336(12):823-7. doi: 10.1056/NEJM199703203361202. PMID: 9062090
  8. Groen, EJ, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann. Surg. Oncol. 2008; 15(9):2439-50. doi: 10.1245/s10434-008-9981-3. PMID: 18612695
  9. Groves, CJ, et al. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut. 2002; 50(5):636-41. doi: 10.1136/gut.50.5.636. http://ncbi.nlm.nih.gov/pubmed/11950808 PMID: 11950808
  10. Gurbuz, AK, et al. Desmoid tumours in familial adenomatous polyposis. Gut. 1994; 35(3):377-81. doi: 10.1016/0959-8049(94)90655-6. PMID: 8150351
  11. Half, E, et al. Familial adenomatous polyposis. Orphanet J Rare Dis. 2009; 4:22. doi: 10.1186/1750-1172-4-22. PMID: 19822006
  12. Hamilton, SR, et al. The molecular basis of Turcot's syndrome. N. Engl. J. Med. 1995; 332(13):839-47. doi: 10.1056/NEJM199503303321302. http://ncbi.nlm.nih.gov/pubmed/7661930 PMID: 7661930
  13. 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
  14. Harach, HR, et al. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994; 25(6):549-61. PMID: 7698732
  15. Harach, HR, et al. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994; 25(6):549-61. doi: 10.1111/j.1365-2559.1994.tb01374.x. http://ncbi.nlm.nih.gov/pubmed/7698732
  16. Hughes, LJ, Michels, VV. Risk of hepatoblastoma in familial adenomatous polyposis. Am. J. Med. Genet. 1992; 43(6):1023-5. PMID: 1329510
  17. Jasperson, KW, Burt, RW. APC-Associated Polyposis Conditions. 1998 Dec 18. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301519
  18. Latchford, AR, et al. A 10-year review of surgery for desmoid disease associated with familial adenomatous polyposis. Br J Surg. 2006; 93(10):1258-64. PMID: 16952208
  19. Leoz, ML, et al. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet. 2015; 8:95-107. doi: 10.2147/TACG.S51484. PMID: 25931827
  20. 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
  21. 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 November 2017.
  22. National Library of Medicine, Genetics Home Reference: Familial Adenomatous Polyposis. http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis Accessed November 2017.
  23. National Library of Medicine, Genetics Home Reference: MUTYH. http://ghr.nlm.nih.gov/gene/MUTYH Accessed November 2017.
  24. Neklason, DW, et al. American founder mutation for attenuated familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(1):46-52. PMID: 18063416
  25. Petersen, GM, et al. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991; 100(6):1658-64. PMID: 1673441
  26. Plail, RO, et al. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg. 1987; 74(5):377-80. PMID: 3036290
  27. 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
  28. Spigelman, AD, et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989; 2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4. PMID: 2571019
  29. Spirio, L, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993; 75(5):951-7. doi: 10.1016/0092-8674(93)90538-2. PMID: 8252630
  30. 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
  31. 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

For management recommendations, please refer to:

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Colorectal 3.2017. ©National Comprehensive Cancer Network, Inc 2016. All rights reserved. Accessed November 16, 2017.

To view the most recent and complete version of the guideline, go online to NCCN.org.

National Comprehensive Cancer Network®, NCCN®, NCCN Guidelines®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
APC* NM_000038.5
MUTYH NM_001128425.1

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.