Genetic Testing Results: Positive, Negative, VUS

Genetic testing for inherited cancer risk does not simply say "yes" or "no." The National Cancer Institute describes several possible results. A result can be positive. It can be negative, which may be a true negative or an uninformative one. Or it can be a variant of uncertain significance.

Knowing what each result means — and does not mean — helps a person understand their risk. It keeps you from reading too much or too little into it.

A result is information to read, not a verdict. What it means depends on your family history.

A positive result means the lab found a change linked to higher cancer risk. This is called a pathogenic or likely pathogenic variant. Pathogenic means harmful.

A positive result can:

• Show, for a person with cancer, that the cancer was likely due to an inherited change. This can sometimes guide treatment.
• Point to a higher risk of certain cancers later. That can guide screening and prevention.
• Give blood relatives information, so they can weigh their own testing

But a positive result cannot say whether or when cancer will start. Some people who inherit a harmful change never get cancer.

A negative result means no harmful change was found with today's tools. What that means depends on the family's history.

• True negative. Sometimes a family already knows about a specific change. If the tested person does not have it, that is a true negative. Their risk is about the same as the general population. That does not mean zero risk. It means this family change is not raising it.
• Uninformative negative. Sometimes there is a strong family history of cancer, but no change has been found in the family. Then a negative result is uninformative. A change may still be there and simply not yet found. Later testing might find it as tools improve.

In both cases, a care team makes sure a person still gets the right follow-up. That follow-up is based on personal and family history.

Sometimes a test finds a change, and there is not yet enough data to know whether it raises cancer risk. This is a variant of uncertain significance, or VUS.

Key points about a VUS:

• Most of the time, a VUS is later reclassified as benign. Benign means it does not raise risk.
• Because it is not known to raise risk, a VUS is usually not used to make health choices. Care is based on personal and family history instead.
• Stay in touch with the provider who ordered the test. That is how you learn if the variant is reclassified later.

Most medical tests tell you only about you. A genetic test can also reveal information about blood relatives. A positive result may lead siblings, children, or parents to weigh their own testing. This is one reason genetic counseling helps, both before and after a test.

A person's genes do not change. So one test usually does not need to be repeated. But the meaning of a result can shift as science moves on. The National Cancer Institute notes that after an uninformative negative, later testing may find a harmful change that was unknown at the time. New genes are discovered, and testing tools get better.

A variant of uncertain significance can also be reclassified later. Most often it is reclassified as harmless. This is why it matters to stay in touch with the provider who ordered the test. It is how you would learn if new information changes what your result means.

Each result carries a specific meaning: positive, true negative, uninformative negative, or VUS. None of them is a simple certainty. The most useful step is to have the result explained. A genetic counselor, or a provider trained in cancer genetics, can tie it to your own history and help plan sensible next steps.