In this blog post, we go over what changed, why it changed, and what it might mean for our users. All of these analyses were performed using the SolveBio API. Python code to perform these analyses is available here.

Assertions and Review Status

ClinVar is a database of reported assertions — these assertions are records of a genetic variant’s (or set of genetic variants’) clinical significance classification for a disease/condition/phenotype. One such assertion might be that a specific missense variant in BRCA2 is pathogenic for hereditary breast cancer.

How do you determine what ClinVar records to use as supporting information during clinical interpretation and research analyses? The piece missing is how that assertion was made. Was this specific assertion determined from experimental studies in one paper, published 20 years ago? Or was this assertion made based on multiple independent observations in patients seen directly by genetic testing clinics?

A ClinVar record’s “review status” is a way of determining how rigorous an assertion is. Previously, ClinVar’s record statuses were relatively simple, with each status corresponding to a number of “stars” for the record on the NCBI ClinVar website. Starting in July 2015, several of the previous review statuses have been split up further (see Table below). The biggest change is that ClinVar submitters are now asked to also submit their “assertion criteria”, or, how the submitter systematically came to their conclusion. This brings a new level of transparency and consistency to ClinVar users.