NCBI Gene: Variations (Part 2): Variants that Affect the Coding Region

To find gene variants associated with disease, you can again start in the NCBI Gene database. From this Gene record for the TH (tyrosine hydroxylase) gene, let's find the single nucleotide variants associated with disease:

Step 1: Use the table of contents to jump to the Variation section of the record.

The Variation section of a Gene record links to several different databases. To find the variants affecting the coding region of this gene that are associated with disease, we'll explore ClinVar.

Step 2: Follow the link to "See variants in ClinVar"

You are now in the ClinVar database, looking at all ClinVar records with TH listed as a gene (the database search is: TH[gene]). Note that these records do not represent all known variants. (We'll get back to that, later.)

We're looking for single nucleotide variants that cause disease.

Step 3: Use the filters on the left hand side under Clinical significance to limit to Pathogenic:

and, under Variation type, select Single nucleotide:

The filters are useful, here, for understanding your results. See, in particular, the "Molecular consequence" filters.

A molecular consequence may be that the coding region is affected. We can see two types of coding consequences, here:

• The "Missense" variants change the codon to be for a different amino acid.
• The "Nonsense" variants change the codon to a codon that ends translation.

Each item in this table of results from ClinVar represents a known variation. The variation is described in a standardized format called the Human Genome Variation Society (HGVS) Nomenclature. There is also brief information here about what conditions the variation is associated with and the strength of evidence on that association. We'll return to this topic in the Clinical section of the course.

For the next part of the tutorial, let's return to the Gene database record to find variants that may not be in ClinVar.

Close both windows to end the Guide.