Test Catalog

Test ID: CDH1Z    
CDH1 Gene, Full Gene Analysis, Varies

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

Confirmation of suspected clinical diagnosis of hereditary diffuse gastric cancer


Identification of familial CDH1 variant to allow for predictive testing in family members


Predictive testing of an asymptomatic child is not recommended.

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

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

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

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant hereditary cancer syndrome associated with germline variants in the CDH1gene,which encodes the protein E-cadherin. HDGC is predominantly characterized by increased susceptibility to diffuse gastric cancer and lobular breast cancer. HDGC is highly penetrant since the risk for developing gastric cancer is 80% by age 80. Women also have an approximately 40% to 60% risk of breast cancer by age 80. Colorectal cancer has been reported in individuals with germline CDH1 variants, however, the specific lifetime risk for colorectal cancer is unknown.


The International Gastric Cancer Linkage Consortium proposes clinical criteria for the selection of individuals who are at increased risk of having a germline CDH1 variant as follows: 1) two or more cases of diffuse gastric cancer (histopathological confirmation in at least 1 case) in first- or second-degree relatives in which at least 1 individual is diagnosed prior to age 50; 2) three or more documented cases of diffuse gastric cancer in first- or second-degree relatives regardless of age of onset; 3) individuals diagnosed with diffuse gastric cancer before the age of 40 regardless of family history; 4) personal or family history of diffuse gastric cancer and lobular breast cancer in first and second relatives with at least 1 diagnosis occurring before age 50.

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

Some individuals who have a diagnosis of hereditary diffuse gastric cancer may have a variant that is not identified by this method (eg, deep intronic alterations, promoter alterations). The absence of a variant, therefore, does not eliminate the possibility of a diagnosis of hereditary diffuse gastric cancer. For predictive testing of asymptomatic individuals, it is important to first document the presence of a CDH1 gene variant in an affected family member.


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


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


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 the interpretation of results may occur if information given is inaccurate or incomplete.

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. Lindor NM, McMaster ML, Lindor CJ, Greene MH; National Cancer Institute, Division of Cancer Prevention, Community Oncology and Prevention Trials Research Group. Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr. 2008;(38):1-93

3. Fitzgerald RC, Hardwick R, Huntsman D, et al: Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010;47:436-444

4. Kaurah P, Huntsman DG: Hereditary diffuse gastric cancer. In: Adams MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews (Internet). University of Washington, Seattle; 2002. Updated March 22, 2018. Accessed August 12, 2020 Available at www.ncbi.nlm.nih.gov/books/NBK1139/

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