Invitae Colorectal Cancer Panel


Test description

The Invitae Colorectal Cancer Panel analyzes genes that are associated with a hereditary predisposition to colorectal cancer. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for colorectal cancer.

Genetic testing of these genes 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 (18 genes)


APC: Deletion/duplication analysis covers the 1A and 1B promoter regions.
BMPR1A: Deletion/duplication analysis covers the promoter region.
EPCAM: Analysis is limited to deletion/duplication analysis
GREM1: Analysis of this gene is limited to deletion/duplication analysis of the promoter region.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.

Add-on preliminary-evidence genes (7 genes)

The BLM, GALNT12, GREM1, POLD1, and POLE genes have been included in the recent NCCN Genetic/Familial High-Risk Assessment Colorectal Guidelines

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Alternative tests to consider

These genes can also be ordered as part a broader, cross-cancer, multi-gene panel. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

  • Cowden and Cowden-like syndrome
  • Familial adenomatous polyposis (FAP)
  • Hereditary diffuse gastric cancer (HDGC)
  • Juvenile polyposis syndrome (JPS)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome
  • MUTYH-associated polyposis (MAP)
  • Oligodontia-colorectal cancer syndrome
  • Peutz-Jeghers syndrome (PJS)

Colorectal cancer (CRC) is a malignancy of the large intestine (colon) and/or rectum. Hereditary colon cancer syndromes are generally divided into two types, Lynch syndrome and polyposis syndromes. Lynch syndrome, also called hereditary non-polyposis colon cancer (HNPCC), is caused by pathogenic variants in MLH1, MSH2, MSH6, PMS2, and EPCAM. This condition is the most common inherited cause of colorectal cancer. Polyposis syndromes are characterized by the development of numerous precancerous polyps, which may become malignant.

Colorectal cancer is the third-most-common cancer diagnosis in the United States, with a general population risk of 4.8%. Although most cases are sporadic and not inherited, approximately 5%-10% are due to an identifiable gene change, which is called a pathogenic variant. Up to 5% of heritable cases are due to Lynch syndrome, less than 1% are due to familial adenomatous polyposis (FAP), and less than 0.1% are due to hamartomatous polyposis syndromes, including juvenile polyposis syndrome (JPS), MUTYH-associated polyposis (MAP), and Peutz-Jeghers syndrome (PJS).

In addition to these conditions, this panel includes other hereditary colon cancer syndromes, many of which are also associated with risks for other types of cancer. Individuals who have inherited a pathogenic variant in one of these genes have an elevated risk of developing cancer, and many of these cancers may be difficult to detect and/or treat. Identifying those at high risk may enable additional screening, surveillance, and interventions, which would result in risk reduction and early diagnosis, thereby increasing the chances of successful treatment and survival.

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 develop 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, download our Cancer risk poster.

All of the genes on this panel have autosomal dominant inheritance for hereditary colorectal cancer. Several of these genes also result in clinically-distinct autosomal recessive conditions, as outlined below:

  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency (CMMR-D).
  • EPCAM is associated with congenital tufting enteropathy (CTE).
  • MUTYH is associated with MUTYH-associated polyposis (MAP).
  • BLM is associated with Bloom syndrome.
  • ATM is associated with ataxia telangiectasia (A-T).

This panel may be appropriate for individuals with a personal history of colon cancer and/or a family history of suggestive of a hereditary colon cancer syndrome, including:

  • an early-onset colon cancer diagnosis at ≤50 years of age
  • multiple primary cancers, including colon cancer
  • colon cancer and a family history of other gastrointestinal or gynecologic malignancies
  • presence of an abnormally high number (10+) of precancerous colorectal polyps (adenomas)
  • multiple hamartomatous colorectal polyps
  • a clinical or family history that meets the criteria for evaluating specific hereditary colon cancer syndromes

There are also some common general features suggestive of a family with hereditary cancer syndrome. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys, both breasts)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., male breast cancer)

  1. American Cancer Society, Lifetime Risks of Developing Various Cancers. Accessed June 2015.
  2. Baglietto, L, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J. Natl. Cancer Inst. 2010; 102(3):193-201. doi: 10.1093/jnci/djp473. PMID: 20028993
  3. Bellido, F, et al. POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet. Med. 2015; :None. doi: 10.1038/gim.2015.75. PMID: 26133394
  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: PMID: 23035301
  5. Briggs, S, Tomlinson, I. Germline and somatic polymerase ε and ō mutations define a new class of hypermutated colorectal and endometrial cancers. J. Pathol. 2013; 230(2):148-53. doi: 10.1002/path.4185. PMID: 23447401
  6. Brosens, LA, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007; 56(7):965-7. doi: 10.1136/gut.2006.116913. PMID: 17303595
  7. Chow, E, Macrae, F. A review of juvenile polyposis syndrome. J. Gastroenterol. Hepatol. 2005; 20(11):1634-40. doi: 10.1111/j.1440-1746.2005.03865.x. PMID: 16246179
  8. Davis, H, et al. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat. Med. 2015; 21(1):62-70. doi: 10.1038/nm.3750. PMID: 25419707
  9. Elsayed, FA, et al. Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer. Eur. J. Hum. Genet. 2014; :None. doi: 10.1038/ejhg.2014.242. PMID: 25370038
  10. Esteban-Jurado, C, et al. New genes emerging for colorectal cancer predisposition. World J. Gastroenterol. 2014; 20(8):1961-71. doi: 10.3748/wjg.v20.i8.1961. PMID: 24587672
  11. Giardiello, FM, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am. J. Gastroenterol. 2014; 109(8):1159-79. doi: 10.1038/ajg.2014.186. PMID: 25070057
  12. Half, E, et al. Familial adenomatous polyposis. Orphanet J Rare Dis. 2009; 4:22. doi: 10.1186/1750-1172-4-22. PMID: 19822006
  13. Han, FF, et al. The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis. DNA Cell Biol. 2013; 32(6):329-35. doi: 10.1089/dna.2013.1970. PMID: 23713947
  14. Hansford, S, et al. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015; 1(1):23-32. doi: 10.1001/jamaoncol.2014.168. PMID: 26182300
  15. Jaeger, E, et al. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat. Genet. 2012; 44(6):699-703. doi: 10.1038/ng.2263. PMID: 22561515
  16. Kempers, MJ, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol. 2011; 12(1):49-55. doi: 10.1016/S1470-2045(10)70265-5. PMID: 21145788
  17. Kohlmann, W, Gruber, SB. Lynch Syndrome. 2004 Feb 05. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301390
  18. Lammi, L, et al. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am. J. Hum. Genet. 2004; 74(5):1043-50. doi: 10.1086/386293. PMID: 15042511
  19. Li, WJ. [Selenium content and glutathione peroxidase in erythrocytes from different populations in areas with high and low mortality of esophageal cancer]. Zhonghua Zhong Liu Za Zhi. 1991; 13(4):265-8. PMID: 1806346
  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. Ma, X, et al. Genetic variants associated with colorectal cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Gut. 2014; 63(2):326-36. doi: 10.1136/gutjnl-2012-304121. PMID: 23946381
  22. Marvin, ML, et al. AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome. Am. J. Med. Genet. A. 2011; 155A(4):898-902. doi: 10.1002/ajmg.a.33927. PMID: 21416598
  23. Mazzoni, SM, et al. An AXIN2 Mutant Allele Associated With Predisposition to Colorectal Neoplasia Has Context-Dependent Effects on AXIN2 Protein Function. Neoplasia. 2015; 17(5):463-72. doi: 10.1016/j.neo.2015.04.006. PMID: 26025668
  24. National Comprehensive Cancer Institute, Who should consider genetic testing for cancer risk? Accessed September 2015.
  25. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. Accessed September 2015.
  26. Neklason, DW, et al. American founder mutation for attenuated familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(1):46-52. PMID: 18063416
  27. Palles, C, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. 2013; 45(2):136-44. PMID: 23263490
  28. Pan, KF, et al. Mutations in components of the Wnt signaling pathway in gastric cancer. World J. Gastroenterol. 2008; 14(10):1570-4. doi: 10.3748/wjg.14.1570. PMID: 18330950
  29. Petersen, GM, et al. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991; 100(6):1658-64. PMID: 1673441
  30. Richards, FM, et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum. Mol. Genet. 1999; 8(4):607-10. doi: 10.1093/hmg/8.4.607. PMID: 10072428
  31. Rivera, B, et al. A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia. Eur. J. Hum. Genet. 2014; 22(3):423-6. doi: 10.1038/ejhg.2013.146. PMID: 23838596
  32. Senter, L, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008; 135(2):419-28. PMID: 18602922
  33. Spier, I, et al. Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas. Int. J. Cancer. 2015; 137(2):320-31. PMID: 25529843
  34. Stenzinger, A, et al. Mutations in POLE and survival of colorectal cancer patients–link to disease stage and treatment. Cancer Med. 2014; 3(6):1527-38. doi: 10.1002/cam4.305. PMID: 25124163
  35. Syngal, S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am. J. Gastroenterol. 2015; 110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. PMID: 25645574
  36. Tan, MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin. Cancer Res. 2012; 18(2):400-7. doi: 10.1158/1078-0432.CCR-11-2283. PMID: 22252256
  37. Thompson, D, et al. A multicenter study of cancer incidence in CHEK2 1100delC mutation carriers. Cancer Epidemiol. Biomarkers Prev. 2006; 15(12):2542-5. PMID: 17164383
  38. Tomlinson, I. Annals Express: The Mendelian colorectal cancer syndromes. Ann. Clin. Biochem. 2015. PMID: 26169059
  39. Umar, A, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J. Natl. Cancer Inst. 2004; 96(4):261-8. doi: 10.1093/jnci/djh281. PMID: 14970275
  40. Vasen, HF, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999; 116(6):1453-6. PMID: 10348829
  41. Weedon, MN, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat. Genet. 2013; 45(8):947-50. doi: 10.1038/ng.2670. PMID: 23770608
  42. Wong, P, et al. Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology. 2006; 130(1):73-9. doi: 10.1053/j.gastro.2005.10.014. PMID: 16401470
  43. Xiang, HP, et al. Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur. J. Cancer. 2011; 47(17):2546-51. PMID: 21807500
  44. van, Lier, MG, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am. J. Gastroenterol. 2010; 105(6):1258-64; author reply 1265. doi: 10.1038/ajg.2009.725. PMID: 20051941
  45. van, der, Post, RS, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J. Med. Genet. 2015; 52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. PMID: 25979631

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

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
ATM NM_000051.3
AXIN2 NM_004655.3
BLM NM_000057.3
BMPR1A* NM_004329.2
BUB1B NM_001211.5
CDH1 NM_004360.3
CHEK2 NM_007194.3
ENG NM_000118.3
EPCAM* NM_002354.2
FLCN NM_144997.5
GALNT12 NM_024642.4
GREM1* NM_013372.6
MLH1* NM_000249.3
MLH3 NM_001040108.1
MSH2* NM_000251.2
MSH6 NM_000179.2
MUTYH NM_001128425.1
PMS2 NM_000535.5
POLD1 NM_002691.3
POLE NM_006231.3
PTEN* NM_000314.4
SMAD4 NM_005359.5
STK11 NM_000455.4
TP53* NM_000546.5

APC: Deletion/duplication analysis covers the 1A and 1B promoter regions.
BMPR1A: Deletion/duplication analysis covers the promoter region.
EPCAM: Analysis is limited to deletion/duplication analysis
GREM1: Analysis of this gene is limited to deletion/duplication analysis of the promoter region.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.