Approving ClinGen Curated Human Variant Data (Decision Summary)

Policy Details

Policy Details

Last Action
Approval Issued
Date of Last Action
Dec 4 2018
Date Introduced
Dec 4 2018
Publication Date
Jan 22 2019

SciPol Summary

On December 4, 2018, the Food and Drug Administration (FDA) recognized the first public database with information about genes, genetic variants, and genetic relationship to disease. This recognition was released in the document “Genetic Database Recognition Decision Summary for ClinGen Expert Curated Human Variant Data,” in which the FDA qualifies ClinGen as a database for genetic and genomics. The FDA based this decision on recommendations set forth in the April 2018 FDA final guidance, “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-based In Vitro Diagnostics.” This final  guidance provides recommendations to ensure a database’s data quality, validity of the genotype and phenotype connections, and safe and accurate scientific evidence is disseminated.

The National Institutes of Health (NIH) funded the development of a database called the “ClinGen Expert Curated Human Genetic Data,” housed within the ClinGen consortium. This database contains information about genes, their variants, and their relationship to hereditary disease. Before ClinGen could qualify as an FDA recognized database, the FDA verified that the database established accurate, reliable, and safe associations between genotypes and phenotypes.

The FDA’s decision summary is divided among two parts. In the first half, ClinGen details how they recruited a team of expert scientists in gene function and biocurators; this team interpreted the clinical significance of genetic mutations. This expert panel uses standards set by American College of Medical Genetics and Genomics (ACMG) guidelines. In the second half, the FDA evaluated ClinGen’s procedures by analyzing three variant assertions: Inherited Cardiomyopathy, RASopathy, and phenylalanine hydroxylase. The FDA looked at the confidence of each ClinGen’s classification and if the information is comparable to what the FDA would evaluate for clinical validity. The FDA then decided that ClinGen uses strong scientific evidence and appropriate methods to classify genetic mutations and their associated disease phenotypes. Not only is the database accurate, but it meets the requirements of public accessibility, privacy for health information, and data security. 

As ClinGen is further developed, the FDA hopes that its value will further increase. This database is freely accessible to the public and may be used as a reference source to validate results found in genetic tests or research. The FDA hopes that the recognition of this database will help researchers learn about new diseases, clinicians provide better healthcare, and pharmaceutical companies develop improved treatments. ClinGen might also be used to subset different genetic variants and provide more individualized treatment plans. As the ClinGen protocols evaluate variant data in the same way the FDA would, this would allow ClinGen to provide evidence to the clinical validity of other genetic tests for future FDA premarket submissions.  

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