avatar

An inconclusive genetic test result: what does it mean?

Questions you can ask to help understand

An inconclusive genetic test result is called a VUS, for genetic variant of unknown significance

Genetic test results are either positive, negative, or less commonly, VUS. This stands for genetic variant of unknown significance.

Most results of genetic testing for inherited susceptibility for cancer are either negative (meaning no gene mutation or change was found) or positive (meaning a gene mutation that causes an increased risk for cancer was found). However, a small portion of tests result in an inconcolusive genetic test result, or what is termed a variant of unknown or uncertain significance, or VUS.

A VUS is a change in the normal sequence of a gene, where the significance of the change is unclear until further study of a sufficiently large population. Complete gene sequencing often identifies many variants for a given gene.

When a VUS is found during a test for inherited susceptibility to cancer, it is unclear if an inherited cancer risk runs in the family. This can be very frustrating for patients, as many patients are hoping that the genetic testing will give information about future cancer risks and also help identify other family members that can be at increased risk for developing cancer.

Question to ask about a VUS genetic test result

When a VUS genetic test result is identified, there are several avenues that can be explored to help determine whether the VUS is associated with an increased risk for developing cancer. Some of them include:

  1. Does the VUS track with cancer in the family? If yes, then this is additional information that the VUS may be associated with an increased risk for developing cancer. If not, than this is additional information that the VUS may not be associated with an increased risk for developing cancer.
  2. Is the VUS seen in both individuals with cancer and without cancer? If yes, then the VUS may not be associated with an increased risk for developing cancer.
  3. Has the VUS been seen in association with a known gene mutation that causes cancer? If yes, then the VUS may not be associated with an increased risk for developing cancer.
  4. Is the area of the gene where the VUS is located in an area of the gene that appears to be important for all species? If yes, then the VUS may be associated with an increased risk for developing cancer.
  5. Is the gene change anticipated to affect how the gene functions in the body? If yes, then the VUS may not be associated with an increased risk for developing cancer.
  6. Is there a loss of the normal gene in tumor analysis? If yes, then the VUS may be associated with an increased risk for developing cancer.
  7. Does the protein seem to function in laboratory studies? If yes, then the VUS may be associated with an increased risk for developing cancer.

If genetic testing identifies a VUS in you, this may not change your treatment or cancer screening recommendations. In addition, it may be recommended that other family members wait until more information is known about the VUS before undergoing genetic testing.

The classification of variants of uncertain significance may change over time as additional information becomes available. Some laboratories do notify the health care provider who ordered the genetic test if there is any reclassification of the variant.

Take the next step:

  • We encourage all our patients who have a VUS genetic test result to keep in contact with our clinic. We can be reached at 734.763.2532.
  • Learn more about genetic testing from the American Cancer Society (PDF).

Sofia Merajver, Kara Milliron

The Breast & Ovarian Risk Evaluation Program at the U-M Comprehensive Cancer Center provides counseling for people with a personal or family history of breast or ovarian cancers that may have genetic links, including BRCA1 and BRCA2. If a link is confirmed, our specialized physicians and genetic counselors will develop a plan for additional screening or lifestyle changes to help reduce your cancer risk.

 

University of Michigan Comprehensive Cancer CenterThe University of Michigan Comprehensive Cancer Center’s 1,000 doctors, nurses, care givers and researchers are united by one thought: to deliver the highest quality, compassionate care while working to conquer cancer through innovation and collaboration. The center is among the top-ranked national cancer programs, and #1 in Michigan according to U.S. News & World Report. Our multidisciplinary clinics offer one-stop access to teams of specialists for personalized treatment plans, part of the ideal patient care experience. Patients also benefit through access to promising new cancer therapies.