NCBI ClinVar

The NCBI ClinVar database collects reports from scientists on human genetic variants and their relationships to disease. Its purpose is to bridge genetic variation data and assertions about phenotypes.

You can search ClinVar with gene symbols, diseases, HGVS expressions, location on a chromosome, and more.

This tutorial is designed to help you answer the question:

How do I find specific disease-causing variants?

Example: What disease or condition is related to the CYP2C9*2 variant?

Over the years, scientists have named gene variants in many different ways. NCBI has attempted to account for these various names by including them in the NCBI database records. Search ClinVar by the information you have, and use the database to uniquely identify the variant of interest.

In this case, we can only assume that CYP2C9*2 is a variant of the CYP2C9 gene. We'll search ClinVar for CYP2C9*2 and see if we can find a record that matches.

Search: CYP2C9*2

[Note: The asterisk (*) is not a wildcard in ClinVar.]

Example: What disease or condition is related to the CYP2C9*2 variant?

You should see 18 or so records in your results for the search of CYP2C9*2 in ClinVar.

This results table provides basic information about the variation, the related gene(s), associated conditions, clinical significance and the review status.

Let's look at the best matching record in more detail.

Click on the link labeled "CYP2C9*2"

Example: What disease or condition is related to the CYP2C9*2 variant?

Let's first focus on the section of the record labeled HGVS. These are Human Genome Variation Society (HGVS) expressions for this variation.

Expand the HGVS section by clicking "more HGVS."

Most ClinVar record titles are in HGVS nomenclature. This record happens to have a different title. But let's break down how to read the HGVS expression:

Looking at the item under Nucleotide starting NM:

NM_000771.4 refers to the reference transcript.

c.430 is the nucleotide position in the coding region of the reference transcript.

C>T means that the C at position 430 of the coding region of NM_000771.4 is changed to a T.

Under the Protein column:

NP_000762.2 refers to the protein reference record.

p.Arg144Cys refers to a resultant amino acid change in the protein.

HGVS expressions are standardized nomenclature for describing variations, so are incredibly useful in communicating about genetic variation. 

MANE Select are high quality transcripts, where the reference sequence from NCBI and that from the European Molecular Biology Laboratories-European Bioinformatics Institute (EMBL-EBI) are identical.

Example: What disease or condition is related to the CYP2C9*2 variant?

Click on the Conditions tab on the left and you will see details of the inherited and pharmacogenomic clinical assertions.

Example: What disease or condition is related to the CYP2C9*2 variant?

The stars reflect the level of agreement on the clinical assertion.

You can view the specific definition of each review status in the ClinVar documentation.

Example: What disease or condition is related to the CYP2C9*2 variant?

You have reached the end of this tutorial on ClinVar.

Close both windows to end the Guide.