Genetic testing is not always a one and done process: the classification of a variant may change over time, technologies improve and better testing may become available; and guidelines and recommendations for testing and management change as we learn new information. This case in “Genetic Testing Challenges in Oncology” highlights some of these issues. The LFSA Genetic Counseling Advisory Group developed the following key points for consideration for those with a variant of uncertain significance (VUS) in the TP53 gene. (April 2026)
- It is important people meet with a healthcare provider or genetic counselor who is knowledgeable about genetic cancer syndromes. These individuals have the expertise in interpreting genetic testing and making sure people get the best possible care based on their personal risk factors and family history.
- The classification of a genetic variant (Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign) can change over time. While classifications generally do not change very frequently they may change as science improves and we learn new things.
- We generally would not expect well-established pathogenic TP53 variants where there are many families and lots of evidence to change classifications frequently, if at all.
- If you have a VUS in TP53 you can check back in with the provider who ordered your testing (or even contact the lab that performed your testing) to ask about the current classification of the variant. It is important to keep your contact information up to date with your testing provider so they can get back in touch with you if they have any important updates.
- Contacting a knowledgeable provider for updates on any genetic testing you have had is important not only for potential reclassifications of a variant, but because over time genetic testing improves and there may be additional testing for which you qualify. Sometimes even when genetic testing for LFS is negative (or shows a VUS) a person may be recommended to undergo additional cancer screening based on their family history of cancer and their personal risks. So, keeping in touch with a doctor or genetic counselor ensures you’re not only getting updates on testing, but also clinical management.
- If you have a variant of uncertain significance (VUS) in the TP53 gene – or uninformative genetic testing – it is very important to let a genetic counselor or your testing provider know about any changes to your personal or family health history – particularly cancer diagnoses – because that information is important both in classifying the genetic variant and in making sure you are being managed appropriately with proper cancer screening recommendations.
