ClinVar: improving access to variant interpretations and supporting evidence

Abstract

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) is a freely available, public archive of human genetic variants and interpretations of their significance to disease, maintained at the National Institutes of Health. Interpretations of the clinical significance of variants are submitted by clinical testing laboratories, research laboratories, expert panels and other groups. ClinVar aggregates data by variant-disease pairs, and by variant (or set of variants). Data aggregated by variant are accessible on the website, in an improved set of variant call format files and as a new comprehensive XML report. ClinVar recently started accepting submissions that are focused primarily on providing phenotypic information for individuals who have had genetic testing. Submissions may come from clinical providers providing their own interpretation of the variant ('provider interpretation') or from groups such as patient registries that primarily provide phenotypic information from patients ('phenotyping only'). ClinVar continues to make improvements to its search and retrieval functions. Several new fields are now indexed for more precise searching, and filters allow the user to narrow down a large set of search results.

Figure 1.

This chart documents the cumulative growth of submissions (A) and organizations that submit to ClinVar (B) since its first public launch in 2013.

Figure 2.

ClinVar holds submissions from >800 organizations, from 60 countries on five continents. See https://www.ncbi.nlm.nih.gov/clinvar/docs/map/ for current counts per country.

Figure 3.

Accessions in ClinVar. Each record submitted to ClinVar is assigned an accession number prefixed with SCV. Submitted records for the same variant and interpreted condition are aggregated into a ‘Reference ClinVar’ record and assigned an accession number prefixed with RCV. Submitted records for the same variant, regardless of disease, are aggregated in a ‘Variation in ClinVar’ record and assigned an accession number prefixed with VCV. VCV records reference the corresponding RCV records and vice versa. Solid lines represent what is aggregated; dotted lines represent what is cross-referenced. In this example, all SCV accessions described a variant that was assigned a Variation ID of 96923 and thus accessioned as VCV00096923. SCV000184036 represents an interpretation relative to a disorder different from that of the others, so it is represented in an RCV distinct from that of the others.