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  • Test code: 01251
  • 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
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Invitae Colorectal Cancer Panel

Test description

The Invitae Colorectal Cancer Panel analyzes genes 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.

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Primary panel (20 genes)

APC AXIN2 BMPR1A CDH1 CHEK2 EPCAM GREM1 MLH1 MSH2 MSH3 MSH6 MUTYH NTHL1 PMS2 POLD1 POLE PTEN SMAD4 STK11 TP53

Add-on Preliminary-evidence Genes for Colorectal Cancer (9 genes)

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.

ATM BLM BUB1B CEP57 ENG FLCN GALNT12 MLH3 RPS20

Alternative tests to consider

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

  • Cowden and Cowden-like syndrome
  • familial adenomatous polyposis (FAP)
  • attenuated familial adenomatous polyposis (AFAP)
  • constitutional mismatch repair deficiency (CMMR-D)
  • hereditary diffuse gastric cancer (HDGC)
  • juvenile polyposis syndrome (JPS)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome – also known as hereditary non-polyposis colorectal cancer (HNPCC)
  • 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%. 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 colorectal cancer syndromes, many of which are also associated with other cancer types. 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 may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial.

For gene-associated cancer risks, download our Cancer risk poster.

Most of the genes on this panel have autosomal dominant inheritance. Several also have autosomal recessive inheritance, or result in clinically distinct autosomal recessive conditions, as outlined below:

  • MSH3 is associated with MSH3-associated polyposis
  • NTHL1 is associated with NTHL1-associated polyposis
  • MUTYH is associated with autosomal recessive MUTYH-associated polyposis (MAP)
  • MLH1, MSH2, MSH6, and PMS2 are associated with constitutional mismatch repair deficiency (CMMR-D)

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)

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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.

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
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
CEP57 NM_014679.4
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
MSH3 NM_002439.4
MSH6 NM_000179.2
MUTYH NM_001128425.1
NTHL1* NM_002528.6
PMS2 NM_000535.5
POLD1 NM_002691.3
POLE NM_006231.3
PTEN* NM_000314.4
RPS20 NM_001023.3
SMAD4 NM_005359.5
STK11 NM_000455.4
TP53* NM_000546.5

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.
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).
NTHL1: Deletion/duplication analysis is not offered for this gene.
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.