NCBI offers a portfolio of medical genetics resources to help you research, diagnose, and treat diseases and conditions. You can easily access our data and tools through the Medical Genetics and Human Variation page of the NCBI website. We also encourage you to join our community of thousands of submitters and share your germline and/or somatic data to advance discovery and optimize clinical care.
How and why should you use our resources? Consider the example below.
Your patient is a 40-year-old mother of two presenting with changes in bathroom habits, bleeding, and belly pain. She has a medical history of colonic polyps. Her family history reveals that her maternal grandmother, mother and uncle had several forms of cancers including colon, breast, and endometrium.
Wondering why 2,100 submitters from 83 countries have deposited more than 1.9 million records of their latest variation information in ClinVar? Curious about why genetic counselors, physicians, researchers, and so many others enthusiastically use data for nearly 1.2 million unique variants in ClinVar? Thinking about becoming part of this global community and sharing your knowledge to further science and make an impact on patient health? Well, we thought we should help you along by making the case for why everyone should submit to ClinVar.
#1: Every deposit can help a patient
The healthcare community relies on the standardized view offered by ClinVar variant reports, which include interpretations of clinical significance in relation to Mendelian disease, cancer and pharmacogenetics; an aggregated view of interpretations highlighting those in consensus, conflict or reviewed by expert panel; and detailed views of submitter data, including supporting evidence for the interpretation such as phenotype, assertion criteria and references.
Now it’s easier than ever to access all data in ClinVar for a variant or set of variants across all reported diseases. ClinVar’s new XML is organized by variant only (Variation ID), instead of the variant-disease pair. This reduces redundancy, for example in cases where a variant is related to several disease concepts, and makes the XML consistent with the ClinVar web pages. You can get ClinVarVariationRelease XML from the /xml/clinvar_variation/ directory on the ClinVar FTP site. New features in ClinVarVariationRelease XML shown in Figure 1 include:
Explicit elements to distinguish between variants that were directly interpreted and “included” variants, those that were interpreted only as part of a Haplotype or Genotype. The clinical significance for included variants is indicated as “no interpretation for the single variant”.
Explicit elements to distinguish records for simple allele, haplotypes, and genotypes
The Replaces element that provides a history and indicates accessions that were merged into the current accession.
A section that maps the submitted name or identifier for the interpreted condition to the corresponding name used in ClinVar and the MedGen Concept Identifier (CUI)
Figure 1. ClinVar variant-centric XML showing a variant record for a haplotype (VCV000236230) that comprises two included variations (SimpleAlleles) that are marked as “no interpretation for the single variant”. The record includes all the condition records (RCVList) with names and identifiers from MedGen, OMIM and other sources.
To learn more about how to use this data, read our documentation.
If you’ve been searching in ClinVar, you might have noticed search improvements introduced in December that reliably connect you with information on your variant of interest. ClinVar has broadened its search capability to accept many different ways of expressing the same variation, including variation described on RefSeq transcripts and proteins. If your variant expression is not reported in ClinVar, we alert you to other variants at the same genomic location or link you to related information in other NCBI resources such as dbSNP, LitVar, and PubMed. ClinVar will also now interpret expressions that contain minor errors or warn you about improper syntax that it cannot interpret.
Figure 1. Improved search results in Clinvar showing mapping of an HGVS expression to the equivalent variant in ClinVar.
Here are some example queries that show the improved search results.
NM_001318787.1:c.2258G>A – an HGVS expression that is not in ClinVar, but ClinVar has an alternate expression for a variant (Figure 1).
NM_004958.3:c.7365C>A – a variant not in ClinVar, but another variant is at the same genomic location is in ClinVar.
NM_002113.2:c.19delG – a variant is not in ClinVar, but there is additional information for the variant in other databases.
We welcome your feedback on your search experience and any additional ideas on how to improve searching in ClinVar.
MedGen is a free, comprehensive resource for one-stop access to essential information on phenotypic health topics related to medical genetics as collected from established high-quality sources. It integrates terminology from multiple primary ontologies (or nomenclatures) to facilitate standardization and more accurate results from search queries.