ClinVar: public archive of interpretations of clinically relevant variants

By M. Landrum, Jennifer M. Lee, M. Benson, Garth R. Brown, Chen Chao, Shanmuga Chitipiralla, Baoshan Gu, Jennifer Hart, Douglas Hoffman, J. Hoover and 9 more. 2015

2,596 citations recorded by the source corpus.

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM®, GeneReviews™, UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands (2022, positive): “In turn, this would be likely to block dynamic sampling of the V U conformation and explains why the S411L mutant cannot signal upon stimulation with p3dsRNA ligands.”
Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines (2017, background): “Missense variants constitute a major set of variants of uncertain significance (VUS) in ClinVar [5].”
New approach for understanding genome variations in KEGG (2018, methodology): “The KEGG VARIANT database also contains links to outside databases such as ClinVar (5), dbSNP (6) and COSMIC (7).”
Settling the score: variant prioritization and Mendelian disease (2017, background): “The common terminology that the Sequence Ontology provides for describing variant effects enables the comparison of annotations across tools, and Sequence Ontology terms are used by most genetic variant databases, such as ClinVar, dbVar, dbSNP and Ensembl Variation 17,28–30 .”
Genomic diagnosis for children with intellectual disability and/or developmental delay (2016, methodology): “We also searched for all those variants listed as pathogenic or likely pathogenic in ClinVar [6], regardless of inheritance or affected status.”
A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. (2019, positive): “, 2017), Clin-Var (Landrum et al., 2016), and avsnp (based on dbsnp 150).”
ClinVar: improving access to variant interpretations and supporting evidence (2017, background): “ClinVar (1,2) is a freely available, public archive of human genetic variants and interpretations of their significance to disease.”
Genome-wide prediction of disease variants with a deep protein language model (2022, methodology): “The first dataset contains variants annotated as pathogenic or benign according to ClinVar [10].”
The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies (2017, neutral): “OMIM does not provide statistics for allelic variants on its website; however, 25,115 germline OMIM variants appear to have been added to ClinVar, which itself currently contains a total of 53,211 pathogenic or likely pathogenic germline variants, whereas dbSNP contains 49,675 pathogenic or likely p”
Selective RNA targeting and regulated signaling by RIG-I is controlled by coordination of RNA and ATP binding (2016, background): “Using the UCSC Genome Browser (42), we found two observations of a serine 411 mutation to leucine (S411L) in large intestine and malignant melanoma tumor samples, annotated in the COSMIC and NCBI ClinVar databases (43,44).”