Peer-reviewed publication examines the benefits of proactive exome reanalysis on diagnostic outcomes
Ambry Genetics, now a wholly owned subsidiary of Tempus AI, Inc., and a leader in clinical genomic testing, today announced the publication of a study in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG). The study reveals the potentially transformative impact of Ambry Genetics’ Patient for Life™ program, which systematically reanalyzes data from the company’s database of exome test results. By reclassifying genetic variants based on newly discovered gene-disease associations and emerging evidence supporting variant pathogenicity, the program may offer renewed hope to patients and families facing undiagnosed rare diseases. Over the study period, 5% of initially negative or uninformative case results that received proactive reanalysis led to a diagnosis.
The term “rare disease” comprises more than 7,000 diseases, each affecting fewer than 200,000 Americans, collectively impacting 25 million to 30 million individuals.1 Exome sequencing tests – which examine the coding regions of genomic DNA – are typically indicated for evaluating children with congenital birth defects, intellectual disability, and neurodevelopmental disorders such as autism spectrum disorder and epilepsy.2 Ambry Genetics was the first commercial laboratory to begin offering clinical diagnostic exome sequencing testing in 20113, which may bring new hope to thousands of patients and families searching for the underlying genetic cause of rare, undiagnosed diseases.
Ambry Genetics’ Patient for Life program is supported by a dedicated team of scientists who continuously analyze emerging data on gene-disease associations and variant pathogenicity. This evidence is then used to reanalyze data from previously tested individuals, providing proactive reporting of clinically relevant findings. This systematic approach helps alleviate the burden on clinicians to request exome reanalysis. As demonstrated in the Genetics in Medicine study analyzing exome cases from 2012 to 2021, 23% of cases underwent at least one reanalysis, with 5% of initially negative or uninformative case results moving from ‘unsolved’ to ‘solved.’ Among cases where lab-driven reanalysis occurred via Ambry Genetics’ Patient for Life program based on newly published data, 54% led to a diagnostic reclassification, compared to just 4% of reanalyses completed following clinician requests. Furthermore, of the reanalyzed cases that led to diagnostic reclassification, 80% involved the identification of a new diagnosis that may have been delayed or missed without the laboratory-initiated Patient for Life reanalysis workflow, highlighting the program’s efficiency in helping providers deliver timely and accurate diagnoses.
“Following a multi-year diagnostic journey, Ambry Genetics’ Patient for Life program helped my son receive a diagnosis for his rare disease more than a year after his initial exome test when new research established the clinical significance of his ZMYM2 mutation,” said Jordan Hinrichs. “Without this program, we might still be searching for answers. Discovering the cause of my son’s condition brought immense relief—and opened the door to a community of families on the same journey. This program didn’t just provide a diagnosis. It gave us connection and hope.”
Tom Schoenherr, CEO of Ambry Genetics, emphasized the importance of the program: “With more than 100 new gene-disease associations discovered every year, this study underscores the necessity of the work our scientists do to support patients seeking rare disease diagnoses. Unlike some laboratories who provide limited or only clinician-driven reanalysis services, we believe we have a responsibility to patients to proactively update clinical reports as new clinically relevant scientific discoveries are made, which may benefit the patients who need answers.”
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