What is a Variant of Uncertain Significance?

Transcription produced by Nellie Maloney

Have you been screened for a genetic predisposition towards breast cancer? I have. My results returned a "Variant of Unknown Significance," or VUS.

What is a Variant of Unknown Significance?

It’s a common question and I am pleased to have Dr. Mártir-Negrón, a medical geneticist at Miami Cancer Institute, part of Baptist Health South Florida, and trained in internal medicine, genetic diagnosis and the treatment of patients with hereditary disorders to help answer this question!

Laura: Dr. Mártir-Negrón, I understand when we get our genetic testing back and read through the results, sometimes we get what is called a variant of unknown significance, also referred to as VUS. Can you explain what this means and how it impacts breast cancer treatment decisions?

Dr. Mártir-Negrón: What a variant of unknown significance means is that there was a change that was found in you. But guess what, we all have changes in our genes; that’s what makes us unique and who we are. The only ones that we know will cause problems are the ones that we call pathogenic.

Based on data, we know that 90% of these inconclusive changes are benign. At the lab we'll continue to review, and when there is more data, they will reach out to whoever ordered the test to inform them of any new findings. The person who ordered the test is the one that is going to receive the reclassification. Again, 90% of the cases are benign, so we call it negative until proven otherwise.

In terms of treatment, we don't do anything with that information and no action is taken. But, if we give recommendations, it's not because of the inconclusive work, it’s what we're seeing in terms of one’s family history. With the inconclusive result, you're always going to have that change, you were born with that change. What it changes is our interpretation.

When we see that somebody has a variant of unknown significance or is inconclusive, we look at ClinVar. ClinVar is a part of the National Institute of Health and aggregates information about genomic variation and its relationship to human health. Obviously, no names or personal data are disclosed. What we do is when we see any inconclusives, we will look at ClinVar to see what all the labs are saying.

Laura Carfang: That's such a great point. ClinVar is a freely available public archive of human genetic variations and interpretations of the relationships to disease and other conditions.

Abigail Johnston: Just another reason why talking to the right doctor about the right topic is so important. Dr. Mártir-Negrón is a geneticist, you don't mind saying you don't know, whereas other doctors in other specialties often avoid saying "I don't know something" and it's very important to remember that.