The new ClinVar

The new design for ClinVar pages is now our default view!  Thank you for the feedback on the new design while it was under development. The redesigned pages have several new features described in a previous post.  The current post highlight some of these improvements in the new ClinVar including the separate variant and condition views, retrieving specific versions of records, and support for ClinVar variant accessions and XML in the E-Utilities .

Using the New ClinVar Pages variant (VCV) and condition views (RCV)

One important improvement in ClinVar is the separate variant-centric  and condition-centric views represented by (VCV) accession number and the (RCV) accessions respectively. The VCV record shows ClinVar data aggregated by a variant or set of variants (haplotype). The RCV aggregates conditions reported for a particular variant or set of variants.  These two pages are especially useful in cases where there are different interpretations for a variant as the examples below show.

BRCA2 variant: hereditary breast and ovarian cancer

Variants in the BRCA2 gene may cause hereditary breast and ovarian cancer.  However, there are many different terms that represent “hereditary breast and ovarian cancer” or related conditions. If you look at an RCV record for only one term, such as “Breast ovarian cancer, familial, 2”, you may only see that the variant has been interpreted as Likely pathogenic. Using the VCV record, you can view all of the interpretations for this variant, so that you see that the variant has been interpreted as both Likely pathogenic for “Breast ovarian cancer, familial, 2” and Uncertain significance for “Hereditary breast and ovarian cancer syndrome” (Figure 1).  Aggregating conditions on the VCV record makes it clear that the variant is pathogenic for some forms of hereditary breast cancer

Figure 1. Aggregating by condition on the VCV record for NM_000059.3:c.67G>A  makes clear that the variant is likely pathogenic for some forms of hereditary breast cancer even though the interpretation is uncertain for a one breast cancer syndrome.

SCN5A variant: Brugada syndrome and Long QT syndrome 3

Variants in the SCN5A gene may cause two different arrhythmogenic disorders: Brugada syndrome and Long QT syndrome 3.  For the coding region variant VCV000067672.1,  you can see that there seem to be conflicting interpretations of pathogenicity (Figure 2). But when you look at the interpretations for each disorder using the Conditions tab, you’ll see that the these apparently conflicting interpretations are for different disorders (conditions). The variant has been interpreted as Pathogenic for Long QT syndrome 3 (RCV000677695.1) but as Uncertain significance for Brugada syndrome (RCV000638649.1). The RCV records allow you to distinguish different interpretations for different disorders.

Figure 2.  The conditions interpreted for the  variant NM_000335.4:c.1604G>A. The variant has a different interpretation for the two arrythmogenic disorders.

Likewise starting from the point of view of a condition such as Brugada syndrome you could quickly find out that the same variant has been interpreted in different ways for other conditions by linking to the variant report.

Retrieving specific version of ClinVar (accession.version)

ClinVar records have versioned accessions (accession. version) that allow you to retrieve a specific version of  a record.  These work in a similar way to version records in other NCBI molecular resources.  For example you can retrieve the most recent version of a record by searching with the accession without the version, VCV000007105 or retrieve a previous version by searching with the full accession.version, VCV000007105.3.  (Note: Version specific searching  for ClinVar records works only on the ClinVar resource. An All Databases search only retrieves  the most recent version.)

Changes to E-utilities (esearch, efetch, esummary)

The new web pages use ClinVar’s new variation-centric XML as the source of data and new accession numbers, beginning with VCV.   E-utilities for ClinVar also now support VCV accessions and return the new XML format.  You can now use E-Fetch to retrieve the latest VCV record using VCV accession number, an accession.version or a variation ID.

VCV accession:

efetch.fcgi?db=clinvar&rettype=vcv&id=VCV000007105

VCV accession.version:

efetch.fcgi?db=clinvar&rettype=vcv&id=VCV000007105.3

Variation ID:

efetch.fcgi?db=clinvar&rettype=variation&id=14206,41472

We are continually working to improve the display and usability of the website. Please use the feedback button on each Variation page, send us your comments, and let us know how ClinVar has helped you at clinvar@ncbi.nlm.nih.gov.