How Genetic Variants Are Classified and Why Patients Should Stay Up to Date
In the rapidly evolving field of genetics, understanding how genetic variants are classified—and why this classification can change over time—is crucial for patients undergoing genetic testing. Whether you’re navigating the results of a genetic test for an inherited disease, cancer risk, or other health conditions, staying informed about how your genetic variants are classified can make a big difference in your health management and decision-making.
How Are Genetic Variants Classified?
Genetic variants are changes or mutations in the DNA sequence that can occur naturally. These variations can be benign, meaning they have no effect on health, or they can be harmful, potentially leading to disease or health conditions. The classification of a genetic variant plays a critical role in understanding whether the variant is clinically significant, and it helps healthcare providers make informed recommendations about testing, monitoring, and treatment options.
The classification of genetic variants is typically carried out based on specific guidelines set by genetic experts, such as those from the American College of Medical Genetics and Genomics (ACMG). According to these guidelines, genetic variants are categorized into several key classifications:
1. Pathogenic Variants
A pathogenic variant is a genetic change known to cause or significantly increase the risk of a disease. These variants have been well-documented through scientific research, clinical observations, and familial studies, providing strong evidence that they contribute directly to health conditions. For example, certain variants in the BRCA1 and BRCA2 genes are pathogenic and are linked to an increased risk of breast and ovarian cancers.
2. Likely Pathogenic Variants
These variants are highly suspected to be associated with disease, but additional evidence may still be needed to confirm the association. While the likelihood of them being harmful is high, further research or more data may be necessary to fully establish their pathogenic nature.
3. Variants of Uncertain Significance (VUS)
Variants of uncertain significance (VUS) are variants for which there is insufficient evidence to classify them as either benign or pathogenic. These variants are often discovered through genetic testing but require further study to understand their clinical relevance. It is important to note that a VUS result does not necessarily mean a variant is harmful, but it also means it is uncertain and requires ongoing monitoring and research.
4. Likely Benign Variants
A likely benign variant is one that has a high probability of being harmless. These variants are commonly found in the population and do not appear to be associated with disease or health conditions. However, as with other categories, further studies may occasionally change their classification.
5. Benign Variants
A benign variant is a genetic change that is not associated with any health risks. These variants are considered normal genetic variations within the population and do not cause disease. Examples might include common variations in eye color or hair texture, which have no clinical impact.
Why Do Classifications Change Over Time?
Genetic testing is an area of constant advancement, and as new research and data become available, the classification of genetic variants can change. Variants that were initially classified as uncertain or benign can be reclassified as pathogenic as more evidence accumulates, or conversely, a variant that was once thought to be harmful might be reclassified as benign. Here are some key reasons why classifications might change:
New Scientific Research: As more studies are conducted, researchers may discover new links between certain genetic variants and diseases, leading to reclassification. A variant that was once considered of uncertain significance might eventually be linked to a specific condition after further research or larger-scale population studies.
Improved Diagnostic Tools: Advancements in technology allow for more precise genetic sequencing and better methods of studying gene function. With these improved tools, variants that were once difficult to assess may now be more easily classified.
Family History and Clinical Evidence: As more family members undergo genetic testing, clinicians may be able to draw new conclusions about how certain variants affect health. Familial patterns of disease may provide more context for understanding the significance of a particular variant.
Larger Databases of Genetic Information: With the growth of genetic databases, healthcare providers have access to a broader range of genetic information, including how specific variants impact different populations. This helps refine variant classifications over time.
Why Is It Important for Patients to Stay Up to Date?
For patients who have undergone genetic testing, staying up to date on any changes in the classification of their genetic variants is essential for several reasons:
1. Impact on Health Monitoring
The reclassification of a variant as pathogenic or likely pathogenic could prompt a change in how a patient is monitored or treated. For example, if a previously uncertain variant is found to be pathogenic, patients may need additional screenings, preventive measures, or more frequent medical checkups to manage potential health risks. Regularly checking for updates on variant classifications ensures that patients are aware of any new recommendations for health management.
2. Informed Decision-Making
Patients who stay informed about their genetic variant classifications are better equipped to make decisions about their healthcare. If a variant is reclassified as pathogenic, patients may want to pursue preventive measures, consider lifestyle changes, or undergo more targeted medical interventions. Staying updated allows patients to make the best choices for their health based on the most current information.
3. Family Implications
Many genetic variants are inherited, meaning the classification of a variant can have significant implications for family members. If a variant is reclassified as pathogenic, relatives may be encouraged to undergo genetic testing to determine if they carry the same variant. Staying up to date on variant classifications helps ensure that family members are aware of their potential risks and can make informed choices about genetic counseling and testing.
4. Advancements in Treatment Options
As genetic research progresses, new treatments or therapies may become available for conditions linked to specific genetic variants. A variant that was once classified as benign or uncertain may later be associated with a condition that has an effective treatment or preventative option. By staying informed about classification changes, patients can take advantage of new treatment options as they emerge.
5. Reassurance
For patients with variants of uncertain significance (VUS), waiting for additional data or reclassification can be anxiety-provoking. However, staying updated on reclassification may provide psychological reassurance. As more information is gathered and variants are reclassified, patients may gain a clearer understanding of their health risks, which can help reduce uncertainty and anxiety.
How Can Patients Stay Up to Date?
Join Citizen Genetics: Our team provides personalized, curated updates on classification changes, research in your disease area, and therapies or experimental treatments in clinical trials.
Join Patient Support Networks: Many genetic testing companies, health organizations, and patient advocacy groups provide regular updates on new research and variant classifications. Becoming part of these networks can ensure you’re kept informed about important developments.
Regular Follow-Ups: Patients who have had genetic testing should consider regular follow-ups with their healthcare provider and/ or genetic counselor to discuss any updates on their results. This is especially important if new clinical guidelines or reclassifications arise.
Use ClinVar to track your variant of interest.
Conclusion
Understanding how genetic variants are classified and why these classifications can change over time is crucial for patients navigating genetic testing. With the ongoing evolution of genetic science, staying up-to-date on the reclassification of your variants is key to making informed health decisions, optimizing your care, and ensuring that family members are aware of their potential risks. The more knowledge you have, the better equipped you’ll be to manage your health and make the best decisions for you and your family.