Test Catalog

Test ID: APCZ    
APC Gene, Full Gene Analysis, Varies

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

Confirmation of familial adenomatous polyposis (FAP) diagnosis for patients with clinical features

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

When this test is ordered, comparative genomic hybridization will always be performed at an additional charge.


See Colonic Polyposis Syndromes Testing Algorithm in Special Instructions.

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

Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by alterations in the APC gene located on the long arm of chromosome 5 (5q21). Classic FAP is characterized by progressive development of hundreds to thousands of adenomatous colon polyps. Polyps may develop during the first decade of life, and the majority of untreated FAP patients will develop colon cancer by age 40. Typically, there is a predominance of polyps on the left side of the colon; however, other areas of the colon may also be affected. The presence of extracolonic manifestations is variable and includes gastric and duodenal polyps, ampullary polyps, osteomas, dental abnormalities (unerupted teeth), congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoids tumors, hepatoblastoma, and extracolonic cancers. Common constellations of colonic and extracolonic manifestations have resulted in the designation of 3 clinical variants: Gardner syndrome, Turcot syndrome, and hereditary desmoid disease.


Gardner syndrome is characterized by colonic polyps of classic FAP with epidermoid skin cysts and benign osteoid tumors of the mandible and long bones.


Turcot syndrome is characterized by multiple colonic polyps and central nervous system (CNS) tumors. Turcot syndrome is an unusual clinical variant of FAP, as it is also considered a clinical variant of hereditary nonpolyposis colorectal cancer (HNPCC). Individuals with Turcot syndrome have CNS tumors in addition to adenomatous polyps. The types of CNS tumor observed helps to distinguish Turcot-FAP variant patients from Turcot-HNPCC variant patients. The predominant CNS tumor associated with the Turcot-FAP variant is medulloblastoma, while glioblastoma is the predominant CNS tumor associated with Turcot-HNPCC.


Hereditary desmoid disease (HDD) is a variant of FAP with multiple desmoids tumors as the predominant feature. Many patients with HDD may not even show colonic manifestations of FAP. APC germline testing may assist clinicians in distinguishing a sporadic desmoid tumor from that associated with FAP.


Attenuated FAP (AFAP) is characterized by later onset of disease and a milder phenotype (typically <100 adenomatous polyps and fewer extracolonic manifestations) than classic FAP. Typically individuals with AFAP develop symptoms of the disease at least 10 to 20 years later than classically affected individuals. Individuals with AFAP often lack a family history of colon cancer and/or multiple adenomatous polyps. Of note, clinical overlap is observed between AFAP and MYH-associated polyposis (MAP), an autosomal recessive polyposis syndrome typically associated with fewer than 100 polyps. Although the clinical phenotype of MAP remains somewhat undefined, extracolonic manifestations, including CHRPE have been described in affected patients. Given the phenotypic overlap of AFAP and MAP, these tests are commonly ordered together or in a reflex fashion.


See Colonic Polyposis Syndromes Testing Algorithm in Special Instructions for additional information.

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 (ACMG) 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

A small percentage of individuals who are carriers or have a diagnosis of familial adenomatous polyposis (FAP) may have an alteration that is not identified by this method (eg, promoter alterations, deep intronic alterations, biallelic alterations in MYH gene). The absence of a alteration, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of FAP. For carrier testing, it is important to first document the presence of an APC gene alteration in an affected family member.


Rare alterations exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


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.


It is strongly recommended that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Technical Limitations:

In some cases, DNA variants of undetermined significance may be identified.


Due to the limitations of next-generation sequencing, 90% of insertions and deletions up to 28 bases and 38 bases, respectively, can be detected. If a diagnosis of one of the syndromes on this panel is still suspected, consider full gene sequencing using traditional Sanger methods. Single or multiexon deletions as well as whole gene deletions will be detected by array comparative genomic hybridization (aCGH).


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 predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported.


Reclassification of Variants-Policy:

At this time, it is not standard practice for the laboratory to systematically 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 S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

2. American Society of Clinical Oncology. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility Clin Oncol. 2003;21:2397-2406

3. Half E, Bercovich D, Rozen P: Familial adenomatous polyposis. Orphanet J Rare Dis. 2009 Oct 12;4:22

4. Croner RS, Brueckl WM, Reingruber B, et al: Age and manifestation related symptoms in familial adenomatous polyposis. BMC Cancer. 2005 Mar 2;5:24

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