Written by Olivia Vaughn
Genetic testing has become a substantial tool in modern healthcare, helping individuals understand their risk for certain conditions, guide medical management, and make informed decisions about their health. When patients receive their results, they often encounter terms like pathogenic, likely pathogenic, variant of uncertain significance, or benign. These classifications can feel confusing and sometimes overwhelming.
Understanding how laboratories classify genetic variants can help patients make sense of their results and appreciate the scientific process behind them. Genetic counselors play a key role in helping individuals interpret these findings and understand what they mean for themselves and their families.
What Is a Genetic Variant?
A genetic variant is simply a change in DNA. Everyone has thousands of variants, most are harmless, and some even make us unique. However, certain variants can affect how the genes function and may contribute to disease. When a lab identifies a variant, the next step is determining whether it is associated with a health condition. This is where variant classification comes in.
How Labs Classify Genetic Variants
Laboratories use guidelines developed by experts to classify variants into five main categories:
- Pathogenic
- Likely pathogenic
- Variant of uncertain significance (VUS)
- Likely benign
- Benign
These categories help clinicians and genetic counselors understand whether a variant is associated with disease and how it should be used to guide medical care. Let’s dive into what each classification means.
- Pathogenic
A pathogenic variant is known to cause disease. There is strong scientific evidence showing that this variant disrupts the gene’s function in a way that leads to a health condition.
Examples include:
- Variants in BRCA1 or BRCA2 that increase cancer risk
- Variants in genes associated with cardiomyopathy
- Variants that cause cystic fibrosis or sickle cell disease
A pathogenic result often leads to specific medical recommendations or screening.
- Likely Pathogenic
A likely pathogenic variant has strong evidence suggesting it causes disease, but the data is not yet as extensive as for a fully pathogenic variant. In most cases, these variants are treated similarly to pathogenic ones in clinical care.
- Variant of Uncertain Significance (VUS)
A VUS is a variant where the laboratory does not yet have enough information to determine whether it is harmful or harmless. This is one of the most common and most confusing results that patients receive.
A VUS should not be used to guide medical decisions. Over time, as more data becomes available, many VUS are reclassified most often to benign or likely benign classifications.
Genetic counselors help patients understand:
- Why VUS happen
- What to do (and not do) with this information
- Whether family testing may help clarify the variant
With VUS, it is best to check back in with your genetic counselor or provider to see if the variant has been reclassified.
- Likely Benign
A likely benign variant is not expected to cause disease. There may be limited data, but the available evidence strongly suggests it is harmless.
- Benign
A benign variant is considered a normal part of human genetic variation. These variants do not cause disease and require no follow-up.
How Labs Decide on a Classification
Labs use multiple lines of evidence to classify variants, including:
- Population data: How common is the variant in the general population?
- Functional studies: Does the variant effect how the gene works?
- Clinical data: Has the variant been seen in people with the condition?
- Family studies: Does the variant track with disease in families?
- Computational predictions: Do computer models suggest the variant is harmful?
No single piece of evidence is enough on its own but labs weigh all the available information to make the most accurate classification possible.
Why Classifications Can Change Over Time
Genetics is a rapidly evolving field. As new research emerges, labs may update a variant’s classification. For example:
- A VUS may be reclassified as benign once more population data becomes available
- A likely pathogenic variant may be upgraded to pathogenic after additional studies
- New evidence may reveal that a variant previously thought to be harmless is associated with disease
This is why staying in touch with a genetic counselor is important as they can help you understand updates and what they mean for your health.
How Genetic Counselors Help Interpret Variant Results
Genetic counselors play a crucial role in helping patients navigate variant classifications. They provide:
- Clear explanations of what each classification means
- Guidance on whether family members should consider testing
- Support in understanding how results affect medical care
- Updates when variant classifications change
- Emotional support during what can be a stressful process
We’re Here to Help
If you’ve received genetic test results and are unsure what they mean or if you’re considering testing and want to understand the process our team at Chicago Genetic Consultants is here to support you. We’re committed to providing clear, compassionate guidance to help you make informed decisions about your health.
