Methods
We created a list of 69 companies based on suggestions from experts, several hereditary cancer publications, the list of ClinVar top 30 submitters, top 10 Medicare submitters, companies mentioned by the organization Facing Our Risk of Cancer Empowered (FORCE), and the Genetic Testing Registry. We narrowed the list by only including companies that were direct-to-consumer, recommended by experts, or in at least 2 other sources. Our final list is 18 companies[1].
We visited each company’s website and extracted data on their available hereditary test panels. Once we extracted the list of genes from the test panels, we used Import.io (online web scraping tool) to pull data about gene variants of each gene from ClinVar. We compared the list of genes to the list of Gene Validity Curations on Clin Gen as well. The curations on this list are considered out-of-date, and we only included a variable of whether or not the gene appeared on the list.
Number of genes found on at least one of the hereditary cancer panels offered by 18 companies: 706
Figure 1: The number of genes that are tested for by multiple companies
Variants of these genes in ClinVar:
- Total 228,110 for 699 genes that have variants in ClinVar
- Average/Gene: 326 variants
- Range/Gene: 9 to 11,964 variants
- Median (half of the genes have fewer than): 91 variants
Figure 2: Average number of variants in ClinVar by number of companies that test for a gene. (Error bars=95% Confidence Interval)
Figure 3: Clinical Significance[2] of variants in ClinVar for 706 Hereditary Cancer Genes
Relationship to guidelines for hereditary cancer risk assessment
Number of genes included on a clinical guideline for hereditary cancer testing: 35
Number of genes that have a clinical validity evaluation: 137[3]
Note: There is not perfect overlap between the guidelines and the clinical validity assessment. Four genes that are on guidelines are not included in the validity assessment as of April 2020 (RET, HOXB13, RHBDF2, PRSS1).
Figure 4: Relationship between number of companies offering a test and the number of variants in ClinVar, and whether or not genes are included on clinical guidelines and have a clinical validity evaluation. (Error bars=95% Confidence Interval)
Figure 5: Relationship between clinical significance and guidelines (Error bars=95% Confidence Interval)
Figure 6: Network depiction of genes on hereditary cancer tests offered by the 18 companies. A link between genes indicates that they are on a testing panel together. The small circle indicates, roughly, where the 35 genes on clinical guidelines appear. The larger circle indicates, roughly, where the 137 genes that have any ClinGen Gene-Disease Clinical Validity classification.
Increasing proportion of VUS
Increasing # variants
Figure 7: Network depiction of hereditary cancer risk assessment landscape tests for the 18 companies.
- Entire network with GeneDx Xpand panel connections deleted
- Purple lines connect genes on clinical guidelines
- Orange lines connect genes that have any ClinGen Gene-Disease clinical validity classification
Figure 8: Detailed overlap of gene testing for the top 7 companies. Note: The GeneDx Xpanded panel (606 genes) was excluded, and many of the genes on this graphic are also part of that panel. The size of the gene name is relative to the number of variants on ClinVar.
Size is relative to the number of variants on ClinVar
Additional details and visualizations can be viewed at: https://docs.google.com/presentation/d/1M9SzOM_MYH6xHjFRlsfNqqBIUKohjZhWq5UMsPt9A_g/edit?usp=sharing
[1] Ambry, Ancestry, ARUP, Blueprint, Color Genetics, EGL, Fulgent, GeneDx, Helix, Invitae, LabCorp, Mayo, Myriad, Prevention, Quest, University of Chicago, University of Washington, Veritas
[2] https://www.ncbi.nlm.nih.gov/clinvar/docs/clinsig/
[3]There is not perfect overlap between the guidelines and the clinical validity assessment. Four genes that are on guidelines are not included in the validity assessment as of April 2020 (RET, HOXB13, RHBDF2, PRSS1).