Is ClinVar the database of choice for clinical diagnostics?

Limbus Medical Technologies is a medical device manufacturer, our software platform is an approved medical device in Europe and our customers are using our product to diagnose patients. One frequently asked question therefore is:

Which reliable databases can I use for clinical diagnostics?

And, in particular:

How reliable is ClinVar?

In recent months, the overall interest in ClinVar has increased noticeably. On the one hand this is due to significantly increased subscription fees for other established commercial databases. On the other hand, the interest is triggered by news about further development and growth of the ClinVar database. Most notably, Illumina contributed a large proprietary dataset to ClinVar in October 2016 which instantly made Illumina the single largest contributor to ClinVar.

In addition, the ClinGen project aims at systematically reviewing entries in ClinVar and improve the quality of data. ClinGen reports 9044 “expert reviewed variants in ClinVar” by end of August 2017. What does that mean for the overall data collection? ClinVar now contains more than 300,000 variant records according to the publishers.

It may not be surprising that maintainers of commercial databases highlight the inconsistencies and shortcomings of ClinVar. Independent research studies paint a more positive picture underlining the utility of a publicly accessible database. The submission process currently still is not suitable for automated data submission at a large scale lacking quality control.

Apart from issues related to content, there are many technical issues, e. g. regarding representation of genetic variants, that have an impact on data quality. Since we have to deal with these technical challenges on a regular basis, we will dedicate a separate post to them which will be published shortly.

In summary, ClinVar is still incomplete and contains inconsistent assessments. Its data must be verified using independent resources, especially if used in the context of clinical diagnostics.

We address these issues with our data network allexes™ which is integrated into our varvis™ platform. In allexes, we collect complete variant and phenotype data in a standardized, de-identified and automated process across many organizations. allexes is scalable and provides transparency about data quality.

About varvis: the clinical decision support system varvis, designed by Limbus Medical Technologies GmbH, Rostock, Germany, is a cloud-based software system to filter and evaluate genetic sequencing data. The varvis platform significantly increases the efficiency and diagnostic yield in clinical genetics. varvis is a Class I medical device compliant with EU regulations. For more information about varvis, visit http://www.varvis.com.