Landmark Study Reveals Magnitude of Uncertain Results in Clinical Genetic Testing for Hereditary Disease, Points to Evidence-Based Solutions to Reach Definitive Results

Rhea-AI Summary

Invitae announces findings from the largest study on uncertain results from hereditary disease genetic testing. The study highlights the prevalence of variants of uncertain significance (VUS) and the need for detailed clinical information and family studies for proper interpretation. The study also found that the likelihood of identifying a VUS increased with larger gene panels and varied based on race, ethnicity, and ancestry. Over the course of the study, a large number of VUSs were reclassified, impacting more than 160,000 individuals. Invitae has invested in developing machine learning methods to reduce uncertainty in genetic testing results.

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• Invitae announces findings from the largest study on uncertain results from hereditary disease genetic testing. The study highlights the prevalence of variants of uncertain significance (VUS) and the need for detailed clinical information and family studies for proper interpretation. The study also found that the likelihood of identifying a VUS increased with larger gene panels and varied based on race, ethnicity, and ancestry. Over the course of the study, a large number of VUSs were reclassified, impacting more than 160,000 individuals. Invitae has invested in developing machine learning methods to reduce uncertainty in genetic testing results.

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– Findings set to enhance patient care and reduce uncertainty in test results as clinicians advance precision healthcare for hereditary disease –  

SAN FRANCISCO, Oct. 25, 2023 /PRNewswire/ -- Invitae (NYSE: NVTA), a leading medical genetics company, today announced findings from the largest study to date on uncertain results from hereditary disease genetic testing. Published in JAMA Network Open, the study evaluated data from more than 1.6 million individuals undergoing multi-gene panel testing across various clinical specialty areas. This study shares with the medical genetics community a dataset that broadly shows the prevalence and attributes of DNA variants of uncertain significance (VUS) and the approaches that help with reclassifying these variants into definitive results. These results underscore the need for detailed clinical information and results from appropriate family studies to facilitate proper interpretation..

"Uncertainty in genetic testing is frustrating for patients, clinicians and laboratories alike. Variants of uncertain significance are not actionable and are often reported from multi-gene panels, exome or genome sequencing, and other genetic tests," said Swaroop Aradhya, Ph.D., FACMG, senior study author and chief of global medical affairs at Invitae. "This study illustrates the VUS burden in hereditary disease genetic testing across clinical areas, and provides clinicians with useful observations that can inform how they educate, set expectations and manage the care of their patients. This becomes particularly important as genetic testing is increasingly incorporated into professional practice guidelines in medical specialties beyond clinical genetics. Invitae has demonstrated leadership in clinical variant interpretation over the last decade and continues to innovate relentlessly to further advance this science and reduce VUS so that more patients can receive conclusive results."

The study, titled "Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing," found that 41% of its more than 1.6 million participants had at least one VUS. When larger gene panels were ordered, especially those intended for diagnosing rare diseases, the likelihood of identifying a VUS increased. As expected, the VUS rate went up as increasing numbers of genes were tested.

A notable finding in this study was that the prevalence of VUSs differs based on race, ethnicity and ancestry (REA), as well as by age group and clinical area. For example, Ashkenazi Jewish and White individuals had the lowest number of observed VUS per individual, while Pacific Islander and Asian individuals had the highest. Therefore, expansion of  the data used for variant interpretation to populations across the globe are needed to reduce uncertain results for historically underrepresented populations and make genetic testing equitable. In that respect, Dr. Saumya Jamuar Shekhar, M.D., clinical geneticist, KK Women's and Children's Hospital and director, SingHealth Duke-NUS Institute of Precision Medicine in Singapore and a co-author on this study, stated "This publication highlights an important need to improve variant interpretation for populations whose genomes are less understood, such as those in southeast Asia and other regions. As Singapore increasingly invests in genomic medicine to improve healthcare for its citizens, it is critical that we have the means to accurately interpret DNA variants in this population."

Uncertainty regarding a variant's clinical classification can be resolved over time when more evidence becomes available. Over the course of this study's eight-year span, a large number of VUSs were reclassified, impacting more than 160,000 individuals who had been referred for genetic testing at Invitae. Of those VUSs, 1 in 5 were resolved to clinically significant classifications, as defined in guidelines by the American College of Medical Genetics and Genomics. Clinical evidence, including detailed clinical information for the patient and results from family studies, contributed the most to VUS reclassifications. There is a critical need for clinicians to partner closely with laboratories to ensure that detailed clinical information is available for variant classification and follow up family testing is performed whenever appropriate.

Invitae has already performed genetic testing for more than 4 million individuals, and as millions more in the future are referred for genetic testing for diagnosis, screening, or research, it is imperative that sophisticated methods are developed to generate evidence that can help classify DNA variants definitively. Data from this study point to the utility of evidence from computational methods and from clinical evidence, both of which need to be gathered more broadly and consistently. As presented at various national conferences, Invitae has invested heavily in developing state-of-the-art machine learning methods to produce reliable evidence for variant classification that has already contributed to reducing uncertainty in results for more than 300,000 individuals referred for genetic testing at Invitae. 

For more information about genetic testing, visit Invitae. 

About Invitae
Invitae (NYSE: NVTA) is a leading medical genetics company trusted by millions of patients and their providers to deliver timely genetic information using digital technology. We aim to provide accurate and actionable answers to strengthen medical decision-making for individuals and their families. Invitae's genetics experts apply a rigorous approach to data and research, serving as the foundation of their mission to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people.

To learn more, visit invitae.com and follow for updates on Twitter, Instagram, Facebook and LinkedIn @Invitae.

Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's beliefs regarding its study results; and the company's belief that the results are set to enhance patient care and reduce uncertainty in test results as clinicians advance precision healthcare for hereditary disease. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the company's ability to grow its business in a cost-efficient manner; the company's history of losses; the company's ability to maintain important customer relationships; the company's ability to compete; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the risk that the company may not obtain or maintain sufficient levels of reimbursement for its tests; the applicability of clinical results to actual outcomes; risks associated with litigation; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2023. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Invitae PR contact:
Renee Kelley
pr@invitae.com 

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SOURCE Invitae Corporation

FAQ

What did the study by Invitae focus on?

The study focused on uncertain results from hereditary disease genetic testing.

What is the prevalence of variants of uncertain significance (VUS)?

The study found that 41% of participants had at least one VUS.

How does the likelihood of identifying a VUS vary?

The likelihood of identifying a VUS increased with larger gene panels and varied based on race, ethnicity, and ancestry.

What impact did the reclassification of VUS have?

Over 160,000 individuals were impacted by the reclassification of VUS, with 1 in 5 being resolved to clinically significant classifications.

What has Invitae done to reduce uncertainty in genetic testing results?

Invitae has invested in developing machine learning methods to produce reliable evidence for variant classification.