President's Corner - Exome Tests are Not All the Same
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Many think that exome sequencing tests from different labs are basically the same and that the only important differentiator is price. In reality, exome (and genome) sequencing tests vary greatly among labs.
Coverage is one way in which exome tests differ. Sequencing is one of the most expensive components of exome tests. Lower average read coverage reduces lab costs appreciably, but also results in fewer exons covered and more sequence variants missed. At PreventionGenetics our minimum average read coverage is 100X. This ensures good coverage of nearly all captured exons.
Approaches used to interpret sequence variants also differ greatly among labs. Some try to use automated approaches to interpretation. Others rely on interpretations set by other labs. Labs also use personnel with different levels of education and experience to interpret variants. All interpretations at PreventionGenetics are set by doctorate geneticists who all work on site. We utilize many programs and databases to assist in our interpretations, but ultimately our knowledgeable and experienced geneticists weigh the evidence and make the final calls. We also interpret all rare variants in all clinically relevant genes. Other labs restrict the number of variants interpreted to genes thought to be involved in the patient’s clinical features.
There are also many different options for return of results in exome tests. At PreventionGenetics we offer the following options. We also routinely provide Copy Number Variant (CNV) analysis in all of our exome-based tests.
- Pathogenic and Likely Pathogenic Variants in ACMG 59 genes
- Pathogenic and Likely Pathogenic Variants in other genes which are likely to result in Mendelian disease
- Carrier testing
- All de novo variants (trios only) (coming soon)
Since our knowledge of clinically-relevant genes is improving steadily, reinterpretation of exome sequences is particularly important. At PreventionGenetics, we save patient fastq files and excess DNA indefinitely, so that we can optimally reinterpret sequences. We also offer one free reinterpretation within two years of the original test.
Confirmation of sequence variants using alternative technologies also varies among labs. At PreventionGenetics, we have developed Sanger assays (with PCR primers in our freezers) for about half of the exons within clinically relevant genes. Our R&D group is continually developing many new Sanger assays. These Sanger assays are used to confirm the NextGen variants. We also confirm CNV calls before reporting.
Finally, labs differ in their approaches to handling genes which are present in more than one copy per haploid genome (what are often called paralogous genes). Paralogous genes are one of the thorniest problems currently facing testing labs (https://www.preventiongenetics.com/documents/March2017.pdf). At PreventionGenetics we have made special efforts to identify paralogous genes and take great care in reporting variants in these genes.
Once in a while we find something in life, perhaps a coat or a pair of shoes that are just right for us. They fit perfectly, are just the right color and style, and we get them at a really good price. We call such items bargains or great values. I like the following definition for value.
Low quality exome tests at a low price are not good values. High quality tests at a high price are also not good values. What you want for your patients are high quality tests at a fair price. This is what we work very hard at PreventionGenetics to provide. The next time you order an exome test for your patient, consider the great value offered by PreventionGenetics.
Thanks to all of our clients for your business in 2017. Happy Holidays from all of us at PreventionGenetics.