ClinVar at five years: Delivering on the promise

Area of Science:

• Genomics
• Clinical Genetics
• Bioinformatics

Background:

• Genetic testing is increasingly used to diagnose Mendelian, pharmacogenetic, and somatic phenotypes.
• This has led to the discovery of numerous novel variants, necessitating accurate interpretation of their clinical significance.
• Challenges exist in interpreting and presenting the significance of these genetic variants.

Purpose of the Study:

• To describe the ClinVar database as a public resource for sharing variant interpretations.
• To highlight ClinVar's role in aggregating data and promoting transparency in variant interpretation.
• To discuss ClinVar's position in improving clinical genetics interpretations.

Main Methods:

• ClinVar was launched in 2013 at the National Center for Biotechnology Information (NCBI).
• It serves as a public database for sharing variant interpretations and supporting evidence.
• Data is aggregated from clinical laboratories, researchers, and expert panels.

Main Results:

• ClinVar contains over 600,000 submitted records from 1,000 submitters, representing 430,000 unique variants.
• The database encourages submissions reviewed by expert panels to ensure a high standard of interpretation.
• Aggregation of data allows for comparison of interpretations, revealing concordance and discordance.

Conclusions:

• ClinVar has become an essential resource for the clinical genetics community.
• It provides a gateway for submitting medically relevant variants and their interpretations.
• ClinVar is well-positioned to enhance the quality and consistency of variant interpretations in clinical genetics.