Addressing the challenges of VUS in genetic and genomic testing with Heidi Rehm, PhD, FACMG

• Variants of uncertain significance (VUS) are a common result of diagnostic genetic testing and can be difficult to manage with potential misinterpretation and downstream costs, including time investment by clinicians. We investigated the rates of inconclusive results due to VUS from over 1.5 million sequencing test results from 19 clinical laboratories in North America from 2020 – 2021 and found a lower rate of inconclusive test results due to VUSs from ES/GS (22.5%) compared to multi-gene panels (MGPs) (32.6%; p<0.001). The high rate of VUS observed in diagnostic MGP testing warrants examining current variant reporting practices and ideas will be discussed as well as overall strategies to inform the interpretation of VUS.

  Level of Instruction: Intermediate

  

  Only the live session qualifies for CEUs but when possible, we host the recordings on our website and NSGC recommends participants to use their personal email instead of work email addresses to ensure they receive their CEU certificates.

  

  Ambry Genetics is approved as a provider for continuing education program by NSGC and ASCLS P.A.C.E ® Program.

Heidi Rehm, PhD, FACMG | Presenter

Chief Genomics Officer, Department of Medicine, Massachusetts General Hospital

Heidi Rehm is the Chief Genomics Officer in the Department of Medicine and at the Center for Genomic Medicine at Massachusetts General Hospital working to integrate genomics into medical practice. She is a board-certified laboratory geneticist and Medical and Clinical Lab Director of Broad Clinical Labs working to guide genomic testing for clinical and clinical research use. She is a principal investigator of ClinGen, providing free and publicly accessible resources to support the interpretation of genes and variants. Rehm also co-leads the Broad Center for Mendelian Genomics focused on discovering novel rare disease genes and co-leads the Matchmaker Exchange to also aid in gene discovery. She is a strong advocate and pioneer of open science and data sharing, working to extend these approaches through her role as vice chair of the Global Alliance for Genomics and Health. Rehm is also a principal investigator of the Broad-LMM-Color All of Us Genome Center supporting the sequencing and return of results to a cohort of one million individuals in the US and co-leading gnomAD, the Genome Aggregation Database.

Catherine Mayo, MS, CGC | Moderator

Genomic Science Liaison I, Ambry Genetics

Catherine has been with Ambry since early 2022 as the Genomic Science Liaison for the New York Metro region. She worked previously in drug development at Genentech in Northern California and then as a pediatric and primarily oncology genetic counselor at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, NY. She currently serves on the Board of Directors of the New York State Genetics Task Force as Director-at-Large for the Community Outreach subcommittee. Catherine received her Bachelor of Science degree in Genetics and Genomics from the University of California, Davis. She earned her Master of Science degree in Human Genetics from the Joan H. Marks Graduate Program at Sarah Lawrence College and is certified by the American Board of Genetic Counseling.