GeneDx Announces Data Demonstrating that Whole Exome and Genome Sequencing Report Fewer Variants of Uncertain Significance (VUS) than Multi-Gene Panel Testing Published in Genetics in Medicine
August 21 2023 - 7:00AM
GeneDx, a leader in delivering improved health outcomes through
genomic and clinical insights, today announced that Genetics in
Medicine, the official journal of the American College of Medical
Genetics and Genomics (ACMG) has published a peer-reviewed research
analysis resulting from a multi-lab collaboration involving GeneDx.
The study, “The landscape of reported VUS in multi-gene panel and
genomic testing: Time for a change,” evaluated the rate of
inconclusive genetic variants, or variants of uncertain
significance (VUS), reported with multi-gene panels versus exome
and genome sequencing. Study findings concluded that VUS are
reported more frequently on multi-gene panels (32.6%) than exome
and genome sequencing (22.5%).
“The high rates of VUS found with multi-gene panel tests create
an unnecessary burden on clinicians and our hospital systems, and
as the title of the paper suggests, it’s time for a change,” said
Heidi L. Rehm, Ph.D., Professor of Pathology, Massachusetts General
Hospital and lead author. “We must examine our current approaches
to reduce VUS rates while directing clinician resources towards
important VUS follow-up.”
The high rate of VUS observed in multi-gene panel testing
warrants broader adoption of approaches used in whole exome and
genome testing. This is in line with evidenced-based ACMG clinical
guidelines, as well as practice guidelines issued by the National
Society of Genetic Counselors Society (NSGC) that have also been
endorsed by the American Epilepsy Society (AES), which recommend
exome or genome testing over chromosomal microarray or multi-gene
panels as a first-tier test for individuals with congenital
anomalies, developmental delay, intellectual disability, or
epilepsy.1, 2
“The results of this study help to address a long-held
perception that whole exome and genome sequencing introduce more
variants of uncertain significance than multi-gene panels, which
may be a barrier to broader adoption,” said Paul Kruszka, M.D.,
Chief Medical Officer, GeneDx. “These data help reinforce the
benefits and value of exome and genome testing to improve diagnosis
and to help end the diagnostic odyssey for more families.”
Study Design: For this study, 19 clinical
laboratories in North America provided deidentified summary data
from a two-year period (January 1, 2020 - December 31, 2021) for a
collective 1.5 million sequencing test results. Aggregate
statistics were calculated for tests with inconclusive results that
included at least one VUS. Test types such as carrier screening
that do not include reporting VUS were excluded. Panel test results
were grouped based on size (number of genes analyzed). Exome and
genome tests were further categorized based on available family
samples (trio, duo, or patient-only). For some laboratories, test
results were also categorized across twelve broad disease
indications.
Study Results Include: Exome and genome
sequencing tests demonstrated lower rates of reported VUS compared
to multi-gene panel tests. Importantly, the study found:
- Variants of uncertain significance were reported less
frequently on exome and genome sequencing (22.5%) than multi-gene
panels (32.6%).
- The use of trios reduces the rate of VUS for exome and genome
sequencing (18.9%) compared to proband-only or duo testing
(27.6%).
Data from this study was previously presented at the American
Society of Human Genetics (ASHG) 2022 Annual meeting.
About GeneDxGeneDx (Nasdaq: WGS) delivers
personalized and actionable health insights to inform diagnosis,
direct treatment and improve drug discovery. The company is
uniquely positioned to accelerate the use of genomic and
large-scale clinical information to enable precision medicine as
the standard of care. GeneDx is at the forefront of transforming
healthcare through its industry-leading exome and genome testing
and interpretation, fueled by one of the world’s largest, rare
disease data sets. For more information, please
visit www.genedx.com and connect with us on LinkedIn,
Facebook, Twitter and Instagram.
Investor Relations Contact:Tricia
TruehartInvestors@GeneDx.com
Media Contact:Maurissa
MessierPress@GeneDx.com
1 Manickam K, McClain MR, Demmer LA, et al. Exome and genome
sequencing for pediatric patients with congenital anomalies or
intellectual disability: an evidence-based clinical guideline of
the American College of Medical Genetics and Genomics (ACMG). Genet
Med. 2021;23(11):2029-2037. doi: 10.1038/s41436-021-012422 Smith L,
Malinowski J, Ceulemans S, et al. Genetic testing and counseling
for the unexplained epilepsies: An evidence-based practice
guideline of the National Society of Genetic Counselors. J Genet
Couns. 2022 Oct 24. Doi.org/10.1002/jgc4.1646
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