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Positive or Negative? It’s not that simple.

Of course there is a distinction between a positive genetic test result and a negative one. Taking it a step further: the separation between true negative and uninformative negative. And what about those VUS?

What are the possible results of a genetic test for CDH1 mutation?

These terms will help to better understand genetic test results:
· Pathogenic mutation: a mutation known to cause or capable of causing cancer.
· Negative: no mutation found.
· Benign mutation: a variant with no impact on health.
· Variant of Uncertain Significance (VUS): a variation was found, but it is unknown if the change is associated with a greater risk of causing cancer.


A positive test result for a CDH1 gene mutation means that a pathogenic (disease-causing) mutation has been found. This result means that a person has HDGC syndrome. This means that a person is at higher risk for developing diffuse gastric cancer and lobular breast cancer. Risk factors may depend upon several things. Having HDGC syndrome does not mean that a person has cancer, or will definitely develop cancer. It just means that they have an increased risk for developing certain cancers.


A negative genetic test result means that no mutation was found in the CDH1 gene. A negative genetic test result may not provide clear information about one’s cancer risk. A negative genetic test result can have several different meanings depending on the individual and on family circumstances of the person tested. A negative test result may be classified as a “true negative” or an “uninformative negative” result.

True Negative

In a family where a pathogenic mutation in the CDH1 gene has been identified, a negative test result for the known mutation is considered to be a “true negative.” This means that this person is not at risk for developing the cancers associated with HDGC due to the CDH1 gene mutation found in their family, and cannot pass the familial CDH1 gene mutation on to their offspring. This person’s risk for developing these cancers would be the same as that of the general population and other personal risk factors.

Uninformative Negative

In some families with multiple cases of cancer, genetic testing doesn’t reveal any answers. In a family with many cases of cancer where all affected members test negative for a CDH1 mutation; a negative test result may be interpreted as an “uninformative negative.” The term “uninformative” means that the test has provided little new information about your cancer risk Some possible interpretations of this result are:

  1. You may have a mutation in the CDH1 gene, but it was not detectable with the testing technology that was used.
  2. You may have a mutation in another gene that was not analyzed in the genetic test performed on you.
  3. You may not have an inherited risk for cancer at all. The cancer in the family may have been caused by other risk factors.
  4. There may be an undiscovered genetic mutation in the family. Ongoing research may reveal other genes that may be involved in the cause of HDGC syndrome for families that have uninformative test results.

These families are encouraged to remain in contact with their genetic counselors, to update medical history and to be informed of any new genetic tests that may become informative. Family members may wish to consider DNA banking, especially for those family members who have a diagnosis of diffuse gastric cancer and/or lobular breast cancer. DNA banking is inexpensive and easy to do. As research advances in the coming years, the DNA of affected family members will be available for further testing, and may be the key to unlocking the genetic mystery in a family.

Variant of Uncertain Significance (VUS)

Genetic testing found a DNA change in the CDH1 gene, but it is not known if the change (variant) is capable of causing disease, thus leading to an increased risk of cancer, or if it is a benign variation that has no impact on gene function. These kinds of uncertain changes are called variants of uncertain significance (VUS). In some cases additional lab testing can be done, and researchers continue to expand the knowledge base about these VUS gene mutations. Find out more about Variants of Uncertain Significance (VUS) including how to seek further analysis of a VUS.

A specialist in cancer genetics is the best person to interpret genetic test results and help determine whether additional genetic testing may be appropriate for a family. Recommended care and treatment for patients and families will vary depending upon specific CDH1 test results, family history and other factors.

Understand more about the different HDGC families to see where your family fits, and next steps to take.

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