The increasing application of genetic testing for determining the causes underlying Mendelian, pharmacogenetic, and somatic phenotypes has accelerated the discovery of novel variants by clinical ...genetics laboratories, resulting in a critical need for interpreting the significance of these variants and presenting considerable challenges. Launched in 2013 at the National Center for Biotechnology Information, National Institutes of Health, ClinVar is a public database for clinical laboratories, researchers, expert panels, and others to share their interpretations of variants with their evidence. The database holds 600,000 submitted records from 1,000 submitters, representing 430,000 unique variants. ClinVar encourages submissions of variants reviewed by expert panels, as expert consensus confers a high standard. Aggregating data from many groups in a single database allows comparison of interpretations, providing transparency into the concordance or discordance of interpretations. In its first five years, ClinVar has successfully provided a gateway for the submission of medically relevant variants and interpretations of their significance to disease. It has become an invaluable resource for the clinical genetics community seeking guidance from consensus interpretations. Building on the platform of providing transparency and leveraging aggregation of variant interpretations, ClinVar is now well positioned to help the clinical genetics community improve interpretations.
Launched in 2013 at the National Center for Biotechnology Information, National Institutes of Health, ClinVar is a public database for clinical laboratories, researchers, expert panels, and others to share their interpretations of variants with their evidence. The database holds 600,000 submitted records from 1,000 submitters, representing 430,000 unique variants. Building on the platform of providing transparency and leveraging aggregation of variant interpretations, ClinVar is now well positioned to help the clinical genetics community improve interpretations.
ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions ...reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations.
ClinVar: improvements to accessing data Landrum, Melissa J; Chitipiralla, Shanmuga; Brown, Garth R ...
Nucleic acids research,
01/2020, Letnik:
48, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
Abstract
ClinVar is a freely available, public archive of human genetic variants and interpretations of their relationships to diseases and other conditions, maintained at the National Institutes of ...Health (NIH). Submitted interpretations of variants are aggregated and made available on the ClinVar website (https://www.ncbi.nlm.nih.gov/clinvar/), and as downloadable files via FTP and through programmatic tools such as NCBI’s E-utilities. The default view on the ClinVar website, the Variation page, was recently redesigned. The new layout includes several new sections that make it easier to find submitted data as well as summary data such as all diseases and citations reported for the variant. The new design also better represents more complex data such as haplotypes and genotypes, as well as variants that are in ClinVar as part of a haplotype or genotype but have no interpretation for the single variant. ClinVar's variant-centric XML had its production release in April 2019. The ClinVar website and E-utilities both have been updated to support the VCV (variation in ClinVar) accession numbers found in the variant-centric XML file. ClinVar's search engine has been fine-tuned for improved retrieval of search results.
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.
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.
ClinGen — The Clinical Genome Resource Rehm, Heidi L; Berg, Jonathan S; Brooks, Lisa D ...
New England journal of medicine/The New England journal of medicine,
06/2015, Letnik:
372, Številka:
23
Journal Article
Recenzirano
Odprti dostop
The assignment of pathogenic status to genetic variants has been stymied by conflicting study results and lack of a publicly accessible database, such as ClinVar, which is now part of the Clinical ...Genome Resource.
On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy . . .
The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database is a collection of annotated genomic, transcript and protein sequence records derived from data in public ...sequence archives and from computation, curation and collaboration (http://www.ncbi.nlm.nih.gov/refseq/). We report here on growth of the mammalian and human subsets, changes to NCBI's eukaryotic annotation pipeline and modifications affecting transcript and protein records. Recent changes to NCBI's eukaryotic genome annotation pipeline provide higher throughput, and the addition of RNAseq data to the pipeline results in a significant expansion of the number of transcripts and novel exons annotated on mammalian RefSeq genomes. Recent annotation changes include reporting supporting evidence for transcript records, modification of exon feature annotation and the addition of a structured report of gene and sequence attributes of biological interest. We also describe a revised protein annotation policy for alternatively spliced transcripts with more divergent predicted proteins and we summarize the current status of the RefSeqGene project.
The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations ...and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. New resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, IgBLAST, GDV, RefSeq, NCBI Virus, GenBank type assemblies, iCn3D, ClinVar, GTR, dbGaP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.
ClinVar is a freely accessible, public archive of reports of the relationships among genomic variants and phenotypes. To facilitate evaluation of the clinical significance of each variant, ClinVar ...aggregates submissions of the same variant, displays supporting data from each submission, and determines if the submitted clinical interpretations are conflicting or concordant. The unit describes how to (1) identify sequence and structural variants of interest in ClinVar by multiple searching approaches, including Variation Viewer and (2) understand the display of submissions to ClinVar and the evidence supporting each interpretation. By following this protocol, ClinVar users will be able to learn how to incorporate the wealth of resources and knowledge in ClinVar into variant curation and interpretation.
GenomeConnect, the NIH‐funded Clinical Genome Resource (ClinGen) patient registry, engages patients in data sharing to support the goal of creating a genomic knowledge base to inform clinical care ...and research. Participant self‐reported health information and genomic variants from genetic testing reports are curated and shared with public databases, such as ClinVar. There are four primary benefits of GenomeConnect: (1) sharing novel genomic data—47.9% of variants were new to ClinVar, highlighting patients as a genomic data source; (2) contributing additional phenotypic information—of the 52.1% of variants already in ClinVar, GenomeConnect provided enhanced case‐level data; (3) providing a way for patients to receive variant classification updates if the reporting laboratory submits to ClinVar—97.3% of responding participants opted to receive such information and 13 updates have been identified; and (4) supporting connections with others, including other participants, clinicians, and researchers to enable the exchange of information and support—60.4% of participants have opted to partake in participant matching. Moving forward, ClinGen plans to increase patient‐centric data sharing by partnering with other existing patient groups. By engaging patients, more information is contributed to the public knowledge base, benefiting both patients and the genomics community.
The GenomeConnect patient registry engages patients in data sharing of genomic and phenotypic data. This data sharing allows for the dissemination of novel genomic data, sharing of case‐level information, provision of a method to receive variant interpretation updates, and connection of participants with one another and with other stakeholders. By engaging patients, more information is contributed to the public knowledge base benefiting both patients and the genomics community.
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