ClinVar

ClinVar provides a public archive of relationships between human genetic variants and phenotypes to support interpretation of clinical significance.

Key Features:

• Integration with NCBI databases: Links variant records to dbSNP and dbVar for genomic location, leverages MedGen for phenotypic descriptions, and uses human RefSeqs to represent sequence variations.
• Data submission and versioning: Accepts submissions from clinical testing laboratories, research entities, and expert panels and assigns unique accession numbers in the SCV000000000.0 format with update-driven versioning.
• Data aggregation and interpretation: Aggregates records by variant-disease pairs and by individual or sets of variants and records submitted interpretations of clinical significance.
• Conflict identification: Identifies and reports conflicting clinical interpretations associated with specific variants.
• Data accessibility and formats: Distributes data in HTML, XML, VCF (Variant Call Format), and tab-delimited subsets and provides annotation tracks on genomic RefSeqs used by tools such as Variation Reporter.
• Indexed search and filters: Implements indexed fields and filters to support precise querying of the archive.

Scientific Applications:

• Clinical variant interpretation: Supports assessment of pathogenicity and clinical significance for variants encountered in diagnostic testing.
• Genomic analysis and disease association studies: Provides centralized variant-disease associations for use in research on genetic contributions to disease.
• Personalized medicine: Supplies curated variant interpretations and phenotypic associations relevant to individualized clinical decision-making.
• Genome annotation: Serves as a source of variant annotations and annotation tracks for integration into genomic pipelines and tools.

Methodology:

ClinVar integrates submissions from laboratories, research groups, and expert panels, assigns SCV accession numbers with versioning, aggregates records by variant-disease pairs, identifies conflicting clinical interpretations, links data to dbSNP, dbVar, MedGen, and human RefSeqs, provides data in HTML, XML, VCF, and tab-delimited formats, exposes annotation tracks on RefSeqs, and implements indexed fields and filters for search.