Gene Classification

We are committed to offering you clear and accurate information in our results reporting. By leveraging our experience, we have developed a robust system for classifying genes that can give you confidence in your results.

Ambry’s clinical validity assessment criteria 

A major challenge for diagnostic laboratories in the rapidly evolving genomics era is interpreting the clinical validity of a gene-disease association. This is highly valuable to clinicians, since they are navigating important medical decisions based on this information. This is described as “the determination that a particular disease is truly caused by variants in a particular gene and that the specific variant that has been detected is indeed pathogenic.” (Biesecker LG and Green RC, N Eng J Med, 2014). 

Our clinical validity assessment is based on a weighted scoring system guided by the ClinGen gene curation criteria, with points assigned to the relationship between one gene and a single Mendelian disease, based on existing literature and data (Smith ED, et al. Hum Mutat 2017). When assessing the clinical validity of the relationship between a gene and a specific disease, the strongest evidence is previously-reported patients with pathogenic mutations in that gene.  Additional consideration is given to: 

As an illustration of the importance of an up-to-date disease-gene classification system, we recently reported that among patients who underwent clinical diagnostic exome sequencing (DES), 23% of positive findings were within genes that were clinically characterized within two years of clinical reporting (Farwell K, et al. Genet Med, 2015).  

The rapid pace of discovery and intensive curation of our gene database leads us to re-evaluate gene disease associations often. When our clinical validity assessment changes a gene from novel to characterized, all previously reported patients with variants in that gene are re-assessed. This can give you confidence that our system prompts us to issue Ambry-driven reclassification reports to you, as a standard component of our testing services. Reclassification is responsible for 9.4% of our positive diagnostic reports.


Clinical Validity Assesment Results in Multiple Upgrades of Clinical Exome Results

Results of All Reanalysis and Reclassification reports, Jan-May 2016