ClinVar

The ClinVar record display

ClinVar has two types of detailed displays: record and variation. This document describes the record display. ClinVar's default display is for the variation; documentation on the ClinVar variation display and a comparison of the two displays is also available.

The ClinVar record display represents the result of aggregating data from independent submissions referencing the same simple or complex variants relative to the same condition. This aggregation is assigned an accession beginning with the letters RCV, and is assigned a version that increases when the number of submissions or interpretation changes for that record.

In the record display, the content at the top of the page is based on the result of that aggregation, augmented with data from other resources at NCBI such as Gene and dbSNP. The data in the tabbed tables below are organized according to each submission, identified by the accession (begins with SCV) assigned to each submitter's record.

Sections on the page

• Title
• Interpretation
  • Review Status
• Allele Description
• Condition(s)
• Clinical Assertions tab
• Genome View tab
• Evidence tab

Title

The variant and condition for which the variant-level clinical assertion is being made, followed by the date the record was last updated. The title is constructed from the preferred name of the variant, and the condition (if provided) for which the variant was interpreted.

Interpretation

Clinical Significance

The clinical significance of the genotype/phenotype relationship, and when that significance was last evaluated. Values used by ClinVar and GTR are provided here:

https://ftp.ncbi.nlm.nih.gov/pub/GTR/standard_terms/Clinical_significance.txt

A detailed description of the representation of clinical significance in ClinVar and other variation resources at NCBI is also available.  Please note ( compare displays ) that in ClinVar's Variation report, pathogenicity is assessed by a 3-level scale rather than 5-level.

Review Status

The level of review supporting the assertion of clinical significance. Stars provide a graphical representation of the review status as detailed in Table 1.

Table 1. The review status and assignment of stars (with changes made mid-2015)

Based on

Count of submissions represented in the record.  Note: this is the total count, not the count of submissions providing an interpretation.

Record status

The status of the record, whether current, deleted or secondary (merged).

Accession

The RCV accession and version number for the set of assertions about the same combination of variation and condition.

Allele Description

Aggregated information that identifies the allele. This may include the gene(s) in which the allele is found, names and a subset of HGVS representations, with links to other data sources about the allele itself.  These data may come from the submitter, but may also be added by NCBI, especially when the allele can be placed on the genome. Data usually provided by NCBI include:

• HGVS expressions:
  • on the current and previous chromosome sequence (NC accession)
  • on the current NM/NP and RefSeqGene (NG)
  • on the version of the NM/NP annotated on the RefSeqGene (NG), if that is not the current version
  • provided by submitters NOTE : ClinVar does not currently list all possible HGVS expressions for a variant. The ones that are reported are selected according to the criteria above.
• GMAF , the global minor allele frequency calculated by the 1000 Genomes Project.
• Allele frequency from GO-ESP and ExAC.
• Molecular consequence: a calculation of the effect of the sequence change if the allele is in a gene.  If there are multiple splice forms for a gene, the consequence is reported for each reference standard cDNA.  This is not predicted functional consequence, but rather effects on translation or splicing computed from NCBI's gene annotation, or location in UTRs or near a gene.
• Suspect : At least one line of evidence variation calls in this region may be affected by paralogs.

Condition(s)

The name of the condition(s) for which this allele set was interpreted, with links to databases with defining information about that condition.

Clinical Assertions tab

A summary for each individual clinical assertion, including the SCV accession number, the submitter, the review status, clinical significance, allele origin, the method used to determine clinical significance, the molecular consequence of the variant, and references as provided from the submitter.

Genome View tab

A display of the genomic context of the variant in NCBI's SequenceViewer. Each variation cited in the record and placed on the genome is labeled with the accession of the ClinVar record.

Evidence tab

A tabular summary of the evidence supporting the clinical significance provided by each submitter, with options to display more details about each submission. The top table (Summary from all submissions)  provides a synopsis from all submissions. The Details of each submission section provides additional data from each submitter, often including free text summarizing the interpretation of the variant/condition relationship.