What Your Genetic Test Results Actually Mean

By Amanda Shrewsbury, MS, CGC

You took the step. You met with a genetic counselor, decided to move forward with testing, and now you're waiting for results, or you've already received them and aren't sure what they mean. Either way, this post is for you.

Genetic test results aren't as simple as "positive" or "negative." There are multiple possible outcomes, and understanding what your genetic test results actually mean depends on your personal and family history. This is one of the most important parts of the genetic counseling process, and it's exactly what your counselor is trained to help you with.

Whether you're someone exploring your hereditary cancer risk proactively, or you were tested because of a recent cancer diagnosis, the categories below apply the same way. What changes is what you and your medical team do with the information.

How Are Genetic Test Results Classified?

When a laboratory analyzes your DNA, they look at specific genes associated with hereditary cancer risk. For each gene, they examine the DNA sequence and compare it to what's considered typical. Any differences they find are called variants.

Not all variants are meaningful. Most are completely harmless. To sort out which ones matter, clinical laboratories use a standardized five-tier classification system developed by the American College of Medical Genetics and Genomics (ACMG):

Benign (clearly not harmful)
Likely benign (almost certainly not harmful)
Variant of uncertain significance (VUS) (not enough evidence yet to classify)
Likely pathogenic (almost certainly harmful)
Pathogenic (clearly harmful)

Your genetic test report will typically focus on categories 3 through 5, since benign and likely benign variants don't change your medical care. Let's walk through what each of the clinically relevant results means.

What Does a Positive Genetic Test Result Mean?

A positive genetic test result means the laboratory identified a variant classified as pathogenic (disease-causing based on strong scientific evidence) or likely pathogenic (disease-causing with a high degree of certainty). In clinical practice, both classifications are treated the same way and carry the same recommendations.

What this means for your health depends on which gene is involved and whether you've already been diagnosed with cancer:

If you have not been diagnosed with cancer, a positive result tells you that your lifetime risk for certain cancers is elevated compared to the general population. Your genetic counselor and medical team will work with you to build a personalized plan that may include enhanced screening (such as starting breast MRI at an earlier age or having colonoscopies more frequently), risk-reducing medications, or in some cases, risk-reducing surgery. The specific recommendations depend on the gene involved and your personal and family history.

If you have already been diagnosed with cancer, a positive result can directly inform your treatment. Certain therapies, such as PARP inhibitors, have been specifically designed to target cancers in people with variants in genes like BRCA1 and BRCA2. Your result may also influence surgical decisions, guide screening for other cancer types you may be at elevated risk for, and help your oncology team make more precise treatment choices going forward.

For your family, a positive result has immediate implications. Each of your first-degree relatives (parents, siblings, children) has a 50% chance of carrying the same variant. Once a specific variant is identified in your family, your relatives can pursue cascade testing, a targeted test that looks only for the known family variant. This gives them a clear answer and is typically covered by insurance. Your genetic counselor will provide a family letter you can share with relatives, explaining what was found and what steps they may want to consider.

A positive result can feel overwhelming, but it's important to remember that no decisions need to be made right away. Your genetic counselor will walk you through every option, and together with your medical team, you'll build a plan at a pace that works for you.

What Does a Negative Genetic Test Result Mean?

A negative genetic test result means the laboratory did not identify a pathogenic or likely pathogenic variant in the genes that were tested. This is generally reassuring, but what it means in practice depends on your specific situation.

True negative (also called an informative negative): If a pathogenic variant has already been identified in your family and you tested negative for that specific variant, you very likely did not inherit the elevated cancer risk associated with that variant. Your cancer screening recommendations would generally return to those for the general population, though your counselor may still consider your broader family history.

Uninformative negative: If no one in your family has been tested before, or if an affected family member tested negative, a negative result is less conclusive. There are several reasons this can happen: the hereditary risk in your family could involve a gene that wasn't included on the panel you were tested with, the variant in your family might be in a region of the gene that current technology can't detect, or the cancer pattern in your family may not be caused by a single inherited gene variant at all.

An uninformative negative does not mean you have no cancer risk. It means the test didn't find a specific genetic explanation. Your counselor will discuss what cancer screening is still appropriate based on your personal and family history patterns, and may recommend revisiting testing in the future as panels expand and technology improves.

This distinction between a true negative and an uninformative negative is one of the most commonly misunderstood aspects of genetic testing. It's also one of the most important reasons to receive your results from a board-certified genetic counselor rather than trying to interpret them on your own.

What Is a Variant of Uncertain Significance (VUS)?

A variant of uncertain significance (VUS) is one of the most common and most confusing results in genetic testing. It means the laboratory found a change in your DNA, but there isn't enough scientific evidence yet to determine whether that change increases cancer risk or is simply a harmless normal variation. A VUS should not change your medical management.

Here's what's important to understand about a VUS:

A VUS should not change your medical care. Both the ACMG and the National Comprehensive Cancer Network (NCCN) are clear on this point: a VUS should not be used to make clinical decisions. You should not have surgery, change your screening schedule, or alter your treatment plan based on a VUS alone. Medical decisions should continue to be guided by your personal and family history.

VUS results are common. The more genes included on a testing panel, the higher the chance of receiving at least one VUS. On large multigene panels, VUS rates can range from 10% to over 40% of all tested individuals. This doesn't mean something is wrong. It reflects the fact that human DNA is incredibly variable, and scientists are still cataloging which variations matter and which don't.

Most VUS results are eventually reclassified as benign. As laboratories collect more data over time, they periodically review and reclassify uncertain variants. Research shows that when VUS results are reclassified, approximately 80–90% are downgraded to benign or likely benign, while only about 10–20% are upgraded to pathogenic or likely pathogenic (NCCN, 2025). In other words, the odds are strongly in favor of a VUS turning out to be harmless.

Reclassification can take time. Some variants are reclassified within months; others take years. When a reclassification occurs, the laboratory issues an amended report to your genetic counselor, who will contact you to explain the updated result and whether anything about your care plan should change. This is one of the reasons it's important to keep your contact information current with your counselor's office.

Family members generally should not be tested for a VUS. Since we don't yet know whether the variant is meaningful, testing relatives for it wouldn't provide useful clinical information and could create unnecessary anxiety.

If you receive a VUS result, the best course of action is to follow the screening and prevention plan that your genetic counselor recommends based on your personal and family history, and to stay in touch with your counselor's office so they can reach you if the variant is reclassified in the future.

What Do "Likely Pathogenic" and "Likely Benign" Mean?

You may notice that some results include the word "likely," as in likely pathogenic or likely benign. These classifications reflect a high degree of confidence (typically greater than 90%) but acknowledge that the evidence isn't absolute. In practice, a likely pathogenic variant is managed the same way as a pathogenic variant, and a likely benign variant is managed the same way as a benign one. The "likely" label doesn't mean the result is uncertain. It means the scientific community is being precise about the strength of the evidence.

Why Should Genetic Test Results Come from a Genetic Counselor?

Genetic test results are not self-explanatory. A report that says "pathogenic variant in CHEK2" means very different things depending on whether you have a personal history of cancer, what type of cancer runs in your family, and what other risk factors you carry. A "negative" result might be reassuring in one context and essentially meaningless in another.

This is exactly why genetic counseling exists. A board-certified genetic counselor is trained to interpret your results within the full context of your personal and family history, explain what the findings mean for your health and your family's health, outline your options clearly and without pressure, and coordinate with your other healthcare providers so everyone is on the same page. (Not sure what to expect from that conversation? Read our walkthrough: What Actually Happens During a Genetic Counseling Appointment.)

Receiving results directly from a lab portal or a non-genetics provider without proper counseling increases the risk of misinterpretation, unnecessary anxiety, or inappropriate medical decisions.

What Comes Next

Whatever your result, you leave your appointment with a personalized summary letter that documents your findings, risk assessment, and recommended next steps. This letter is designed to be shared with your primary care physician, oncologist, or other members of your care team.

If you tested positive, your counselor will also provide a family letter to help you share the information with relatives who may benefit from cascade testing.

And if your results were negative or you received a VUS, your counselor will make sure you have a clear screening plan based on what we know today, with a path to revisit as the science evolves.

References

Richards, S., Aziz, N., Bale, S., et al. (2015). Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405–424.
National Comprehensive Cancer Network. (2025). Genetic/familial high-risk assessment: Breast, ovarian, pancreatic, and prostate (Version 2.2025).
Mersch, J., Brown, N., Engel, G., et al. (2018). Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA, 320(12), 1266–1274.