The database created by the Clinical Genome Resource program (ClinGen) has been recognized by the U.S. Food and Drug Administration, FDA commissioner Dr. Scott Gottleib and National Institutes of Health director Dr. Francis Collins announced jointly today.
ClinGen, a NIH-funded program, is a resource that is dedicated to establishing a central database that defines the clinical relevance of genes and variants with the intention of informing precision medicine and research. ClinGen was launched in 2013, with faculty from Baylor College of Medicine playing key roles in developing and advancing the program.
“FDA recognition of ClinGen’s process for interpreting variants, or mutations, found through genetic testing highlights for the genetics community our goal of developing authoritative sources of clinical genetics that is publicly available to them. ClinGen is filling a critical need in the substantial challenge of gathering data and connecting it with the community for use in supporting genomic medicine and research,” said Dr. Sharon Plon, principal investigator on the ClinGen project and professor of pediatrics-oncology and molecular and human genetics, and co-leader of the pediatric cancer program in the Dan L Duncan Comprehensive Cancer Center at Baylor.
ClinGen’s recognition is the first of its kind issued through the new FDA Human Variant Database Program, which seeks to support an easier path for marketing clearance or approval for clinical gene test developers. This recognition enables ClinGen to provide a gold-standard example of an approach for interpretation of inherited genetic variation that other organizations can adopt, and underscores the importance of a consistent approach, collaboration and sharing of knowledge to improve healthcare.
Dr. Aleksandar Milosavljevic, professor of molecular and human genetics at Baylor, and his team have played a critical role in developing the informatic tools and infrastructure to support the interpretation of variants and make the process and evidence available to the public. Particularly relevant parts of the database are the ClinGen Allele Registry and the ClinGen Evidence Repository, both developed by the Bioinformatics Research Laboratory directed by Milosavljevic.
“The Allele Registry enables real-time creation of universal IDs for variants, meaning a given variant can be uniquely referenced by its ID. The Evidence Repository enables sharing of evidence for or against pathogenicity, or the disease association, of variants, along with guideline-based conclusions about their pathogenicity,” said Milosavljevic.
Early examples of ClinGen interpretation included two genes, PTEN and CDH1, which are included in many cancer genetic tests. ClinGen is working to expand the use of cancer genetic data for estimating risk of cancer or the interpretation of genetic changes found in tumors. The ClinGen database provides a resource of human variants that have been interpreted for their potential association with disease, and helps assure that clinical interpretations of genomic test results are accurate.
ClinGen has also assembled expert teams that develop the needed specifications and employ a systematic approach to this variant interpretation and provide evaluations of relevant scientific evidence. ClinGen Variant Expert Panels are international in make-up and include experts from both industry and large academic medical centers to achieve robust, optimized classifications of genomic variation.
This expert knowledge, together with the approach to variant interpretation and the evidence evaluated, is publicly disseminated and made fully accessible to other clinicians and laboratory scientists with the aim of improving the quality of genomic medicine.
Genomic testing is routinely used in clinical care, particularly for the accurate diagnosis of inherited disorders. Scientifically valid methods for assessing the clinical significance of genes and DNA variants is critical for guiding the healthcare for thousands of patients who undergo genetic testing each year
Achievement of FDA recognition is the result of hard work from clinicians, scientists, informaticians and administrators across the ClinGen Resource. Drs. Ronak Y. Patel and Piotr Pawliczek, both with Baylor, participated in the development of the Allele Registry; Dr. Ronak Y. Patel, Andrew R. Jackson and Mr. Sameer Paithankar, all with Baylor, participated in the development of the Evidence Repository. The ClinGen expert curated human variant data are available for unrestricted use in the community via ClinVar, an archive which is funded and maintained by NIH’s National Center for Biotechnology Information, part of the National Library of Medicine. See all of ClinGen's tools.