Article authored and provided by Ambry Genetics as part of a paid partnership with NSGC. The content, views, and opinions expressed in this article are those of Ambry, and do not necessarily reflect the opinions and views of the National Society of Genetic Counselor

If you’re working in a setting where exome testing is routinely ordered, you may recognize some of the ways reanalysis protocols can fall short. Exome reanalysis can be limited by patient compliance with return visits, clinic challenges in scheduling follow-up, the administrative burden of managing requests through one or more laboratories, and uncertainties around cost and patient ability to pay. In addition to these challenges, are you aware that typical reanalysis practices also contribute to increased health disparities?

In recent study data shared at the NSGC 43rd Annual Conference, Andrew Giles, MS, CGC, and coauthors observed the impact of race and ethnicity on the outcomes of exome sequencing and its reanalysis. The results were revealing. Notably, each racial and ethnic group that underwent exome reanalysis saw a marked increase in positive results, demonstrating the value of reanalysis. The study found that minority groups, particularly those of African/Black ancestry, had higher rates of variants of uncertain significance (VUS) and lower rates of diagnostic test results on exome testing. These groups were also less likely to receive reanalysis, but most likely to benefit from it.

At Ambry Genetics, we’ve incorporated an approach for addressing this disparity through the Patient for Life program, which provides laboratory-initiated, proactive reanalysis. The Patient for Life program applies to exome sequencing and neurology panel tests (which are performed on an exome backbone).

It is estimated that a new gene-disease relationship is characterized every 2 days. To stay current, we commit significant resources, including an entire team of clinical scientists, to reviewing the medical literature for the latest findings on gene-disease relationships. When a new gene-disease association is identified, we reanalyze all available exome data at no charge to the patient, and revised reports are issued where new findings apply. Our genetic counseling team contacts the ordering provider to review the new findings. This proactive approach systematically screens all previously reported cases for clinically relevant findings, helping to ensure more equitable access to updated and accurate genetic testing for all patients.

Since its inception, the Patient for Life program has provided clinically relevant reclassifications to 1 in 20 patients with previously negative or uninformative exome results. Gene-disease validity accounts for over half of all exome reclassifications. Because the Patient for Life program is proactive, it is not dependent on patient compliance or ability to pay. It also removes most of the administrative burden on the genetics clinic: the only reanalysis requests you need to manage are those triggered by a clinically significant chance in signs and symptoms. This approach ensures that all patients can get the answers they need. By providing equitable access to new diagnostic information, Patient for Life is helping to bridge the gap in genetic testing outcomes between different racial and ethnic groups and to reduce health disparities for rare disease.

To dig deeper into the study's findings, you can find a full summary in this blog post by study author Andrew Giles.

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