The Importance of Reanalyzing Genetic Test Results for Rare Diseases

Many companies providing diagnostic genetic testing offer reanalysis services “upon customer request.” But how important is this reanalysis? Let’s explore the significance of reanalysis in diagnostic genetic testing through the five-year “daily reanalysis” results conducted by 3billion

Common Questions About Reanalysis

“Isn’t genetic testing a one-time thing?” 

“Why is retesting necessary?” 

“Is retesting different from reanalysis?”

These questions are frequently asked. When undergoing WES (Whole Exome Sequencing) or WGS (Whole Genome Sequencing) tests, people are often informed that “this test only needs to be done once. Your genes won’t change even if you test again.” This is generally true. Reading your genes will almost always show the same nucleotide sequence regardless of when you read them.

The Importance of Reanalysis According to ACMG

This isn’t just our assertion; it is also recommended by the ACMG (American College of Medical Genetics), which provides global guidelines for the interpretation of genetic variants. The ACMG recommends that genetic data for undiagnosed patients be reanalyzed at least once every two years to incorporate new research and findings.

(Check the full statement from ACMG here)

The ACMG emphasizes the importance of continuous reanalysis for several key reasons:

• Evolving Knowledge: New gene-disease associations and improved computational algorithms for predicting pathogenicity continually emerge.
• Phenotypic Changes: Patients’ clinical features can evolve over time, necessitating updates to variant interpretations.
• Technological Advances: Improved bioinformatics tools and methodologies may uncover previously unrecognized variants.
• Data Sharing: Increased data sharing through public databases enhances the accuracy of variant classifications.

These efforts ensure more accurate and clinically relevant genetic diagnoses.

Significance of 3billion’s Reanalysis Service

Recognizing the importance of continuous reanalysis, 3billion has included ‘daily reanalysis’ in all its WES services (3B-EXOME). But was this policy of reanalysis truly meaningful? Did updating new data daily and utilizing analysis resources to reanalyze really help improve diagnosis rates for patients with rare diseases, thereby aiding in better treatment and prescription?

3billion’s Reanalysis Over Four Years Shows More Than Just Utility

Since May 19, 2020, 3billion has applied automated reanalysis to all 3B-EXOME tests. For cases where the reporting results were VUS (Variant of Uncertain Significance) or Negative, meaning no current explanation for the patient’s symptoms could be found, we introduced an algorithm that automatically reanalyzes with new data daily. Over the next five years, we reanalyzed the data of nearly 20,000 patients daily. Thankfully, meaningful updates were made for about 1,080 patients!

Impact of Reanalysis on Diagnoses

We observed all four reasons ACMG cited for the necessity of reanalysis.

• 44% of updates resulted from new research findings on diseases, genes, and genetic variants.
• 39% were due to updates in 3billion’s internal database and pipeline.
• Other reasons included reclassification of variants and additional patient symptoms.

With over 10,000 tests conducted annually, about 1-2% of all tested patients received additional diagnoses through reanalysis. Considering continuous data updates even in standard analysis systems, this is a significant figure.

3billion’s Daily Automated Reanalysis Pipeline

3billion’s daily automated reanalysis pipeline is the result of the combined efforts of our clinical team, bioinformatics team (handling the backend of the pipeline), and software and web development team (handling the frontend).

All these results demonstrate the importance of reanalysis. It has become evident that reanalysis can be a powerful tool in giving hope to undiagnosed patients. 3billion will continue to strive for a good impact by incorporating automatic reanalysis systems into the 3B-GENOME analysis service, continuously improving diagnosis rates.