Invitae Releases Study Highlighting Unknown Variant Rates in Large Genetic Panels
Invitae has released the results of a new study on uncertain findings in hereditary disease genetic testing, revealing the prevalence and characteristics of DNA variants of uncertain significance (VUS). The study examined data from over 1.6 million individuals who underwent multi-gene panel testing across various clinical specialty areas. The study found a large number of patients experienced variants of uncertain significance (VUS) when receiving test results. The study highlighted the need for programs to classify variants of unknown significance.
Uncertain results from genetic testing can be frustrating for patients, clinicians, and laboratories and are common in genetic tests, including multi-gene panels, exome, or genome sequencing. The study, “Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing,” revealed that 41% of participants had at least one VUS, with larger gene panels associated with a higher likelihood of identifying a VUS. One notable discovery from the study was that the prevalence of VUS varied based on race, ethnicity, ancestry, age group, and clinical area. This suggests the need to expand variant interpretation data to historically underrepresented populations to ensure more equitable genetic testing. Dr. Saumya Jamuar Shekhar, a co-author on the study, emphasized the importance of improving variant interpretation for less-understood populations, such as those in Southeast Asia.
Over the eight-year duration of the study, a significant number of VUSs were reclassified, positively impacting more than 160,000 individuals referred for genetic testing at Invitae. Approximately 20% of these reclassifications were resolved to clinically significant classifications, thanks to the availability of detailed clinical information and results from family studies. Invitae has also invested in state-of-the-art machine learning methods, contributing to the reduced uncertainty in results for over 300,000 individuals referred for genetic testing at the company. Myriad Genetics, a competitor to Invitae launched a similar initiative called myVision which is an algorithmic based approach to variant classification validated using data from over 400,000 patients. Ambry Genetics also has an active family studies program to classify variants.