Reporting Variants with Multiple Transcripts

Osman Zuberi
2 min readJan 18, 2021

GenomOncology strives to give our clients the best tools to help them make informed decisions. Our goal as partners to our clients is ensuring the highest quality of patient care, and providing the most accurate information available at the time. This is precisely why we recently introduced the ability to choose from multiple transcripts when reporting variants in the GO Pathology Workbench.

In order to better understand why this feature is so important, we need to understand what the concept of multiple transcripts is. During transcription, the exons of a gene are copied to RNA form, called a ‘transcript’. Despite only having ~20,000 genes, human beings are so complex because of our genes’ ability to produce multiple transcripts, creating different proteins in the body. While this is great for evolution, this can lead to complexity and problems with variant nomenclature. If one lab uses one transcript to define a region, and a different lab uses another, how could they collaborate or understand each other’s data?

When reporting results from NGS sequencing, labs needed a way to describe which particular transcript they were using for a specific gene so that they could solve this problem. The transcripts they choose to use are known as the canonical transcript. Though choosing a canonical transcript makes the problem of describing the same mutation in different ways easier, not all labs agree on which ‘canonical’ transcript should be used, leading us to the use case of alternate transcripts.

If a lab uses a transcript that they consider canonical for a particular gene, why would they ever need to report something using anything else? The answer lies in the difference between the most clinically significant transcripts, versus the most widely used. Certain variants can be more or less important than others depending on what kind of mutation they have. Sometimes a variant’s most significant mutation can be found using the canonical transcript, however, there are times when the most significant mutation is found on an alternate transcript instead. Which is why we’ve introduced a feature to allow users of the GO Pathology Workbench to report variants which have different mutations on multiple transcripts. This way they will be able to illustrate the differences between a canonical and alternate transcript for the same variant, and put this information on a report.

When dealing with these small discrepancies it is extremely helpful to have all of the available information possible so that oncology providers can make the most accurate and informed decisions. GenomOncology believes in our world-class clients abilities to provide the best quality care to their patients. This is why we aim to provide them with the most relevant information, and let them make the best decisions for their patients.