top of page

SDS & Science Snapshots (2024-06-01)

In this issue: What is the difference between germline and somatic genetic testing?

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email or message us on Facebook! This is all for you!

Ask an Expert Recap: The Difference between Germline and Somatic Genetic Testing

At the most recent Ask an Expert webinar in May (see below), we heard from Dr. Lisa J. McReynolds, one of the newest members of the SDS Alliance Medical and Scientific Advisory Board (you can read her biography and more about her work here and welcome to the SDS Alliance community, Dr. McReynolds!). In this meeting, one of the topics discussed was the importance of diagnostic genetic testing for individuals with SDS and how hereditary (germline) variants (or mutations) are different from somatic mutations detected in cancerous (or pre-cancerous) cells, also known as clones. In our SDS & Science Snapshot this week, we will discuss the difference between these two mutation types (and how they are tested for) in more detail.

In the world of cancer, there are two main types of genetic tests that are used to inform care: germline genetic testing and somatic tumor (genomic) testing. Understanding the difference between these two types of mutations can be helpful in navigating the complexities of SDS. In a previous SDS & Science Snapshot, we discussed the difference between germline and somatic variants (or mutations). 

The figure below compares germline genetic testing and somatic genomic tumor testing. Sometimes in the clinic, somatic genomic tumor testing is also referred to as “NGS” (which stands for “next-generation sequencing”) and is frequently performed on the bone marrow biopsy samples from patients with SDS as discussed below.

While the results of these two types of genetic testing often look similar, there are a few key differences in the somatic genomic tumor testing to look out for:

  • Variant allele frequency (VAF): This is how often the variant (or variants) were seen in the tested sample of cancerous (or pre-cancerous) cells. VAF provides insights to how predominant the variant (or variants) may be in the tumor sample. Knowing the VAF of somatic variants detected in a bone marrow biopsy sample can help your care team monitor for the development of MDS or AML or give insight into how someone with MDS or AML is responding to treatment.

    • Key difference: Sometimes germline variants can be identified on somatic genomic testing, but the VAF of germline genetic variants is typically around 50% and, if detected, are generally expected to remain constant across multiple somatic genomic tests. This is in comparison to the VAFs of somatic mutations, which change over time as the clones of cancerous cells develop and evolve over time. 

  • Genes: Some genes are more commonly altered in pre-cancerous or cancerous cells than others. For example, TP53 variants are frequently seen in the bone marrow samples of individuals with MDS or AML, but most of those individuals do not have a germline TP53 variant, or Li Fraumeni Syndrome. Other examples of genes commonly mutated in the bone marrow samples of individuals with MDS or AML include DNMT3A, TET2, CSF3R, SF3B1, IDH1/2, RUNX1, and GATA2.

  • Report Comments: Somatic genomic tumor testing (or NGS) are not meant to detect germline variants. If there is concern for the accidental detection of a germline variant that may play a role in a patient’s care plan, there will often be a comment about this in the NGS report. 

For more information regarding the development of clones and the difference between somatic and germline variants, you can watch this educational video on the genetics of SDS. We cover the concept of germline versus somatic variants (around minute 5), and how they relate to leukemia. You might also find it helpful to watch the recording of the Ask an Expert webinar with Dr. Lisa J. McReynolds above.

We encourage you to ask your healthcare provider about any questions you have about any genetic testing results, germline or somatic, and how these are used to manage care.


For more information regarding the difference between somatic and germline variants, you can visit the Cleveland Clinic’s website.


The SDS & Science Snapshot this week contains content modified from materials in this blog post, Tumor Genetics: Somatic vs Hereditary, published by Quest Diagnostics.


Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:


bottom of page