This is part of a blog series from genetic counselors at the Basser Center. This was written by Jessica Ebrahimzadeh, MS, LCGC.

The field of genetics is constantly evolving. These updates not only apply to the science, but also include changes to terminology used to describe genetic findings. One modification in genetic nomenclature over the past few years, is the use of “variant” in place of “mutation.”

Before describing the terminology transition, here are some basic genetic concepts to help put this in context:

  • Every human has over 20,000 genes. Each gene is responsible for providing instructions for specific functions in our cells and our bodies. These instructions are made up of segments of DNA, which are spelled out in a similar fashion as a sentence.
  • Genetic differences between people, even family members, are common; each person has their own unique genetic makeup. Many times genetic variation may simply exist without any known impacts. Think of the spelling “gray” vs “grey” - it may look a little different, but it means the same thing. Sometimes these genetic differences contribute to hair color, height, or a range of other features that are considered a part of normal human variation.
  • Single gene conditions are caused by a harmful change or mutation in the DNA that cause a specific gene to no longer work correctly, which results in particular features.
    • Example: Every person has two copies of the BRCA1 gene and two copies of the BRCA2 gene. Both of these genes play an important role in DNA damage repair which helps prevent cancer from occurring. If there is a change that stops the gene from working, there is an increased risk for certain cancers, such as breast and ovarian cancer.

So, let’s revisit: what is a gene mutation? A gene mutation simply means there is a change from the reference DNA sequence. By definition, a mutation does not imply the change is damaging, advantageous, or neutral. Although, many deep-seated cultural references have established a negative connotation to the word mutation; this has also lead to the inaccurate assumption that every gene mutation is harmful or disease-causing. This left the genetics community with a need to help categorize genetic changes and also help clearly communicate whether certain genetic mutations are harmful or just simply exist without impacts.

In efforts to avoid confusion, there has been a movement in the genetics community, including a recommendation from a prominent professional organization (American College of Genetics and Genomics), to retire the term “mutation” and replace it with the more impartial noun “variant.” The intent is for “variant” to remain a neutral term, but that modifiers should be added to better describe the how the change may (or may not) impact the gene function. More specifically, variant classifications are applied to single gene conditions and include the following categories: pathogenic, likely pathogenic, uncertain significance, likely benign, or benign.

Pathogenic and likely pathogenic variants have strong evidence to support that the variant is disease causing. In other words, the pathogenic or likely pathogenic variant is expected to cause the gene to no longer work correctly which is considered a “positive” genetic testing result. Conversely, benign or likely benign variants are not expected to impact gene function and have enough evidence to be considered a harmless difference.

While this switch up has been widely accepted in scientific journals and by some clinical genetic testing laboratories, it is still common to hear many people use the word “mutation” interchangeably with “pathogenic variant.” Admittedly, qualifying a variant as “likely pathogenic” or “pathogenic” doesn’t roll of the tongue as easily as it’s three-syllable counterpart. Also, many individuals are simply less familiar with the new terminology. Although adjusting vocabulary will continue to take time, you can anticipate that you may start seeing “likely pathogenic variant” or “pathogenic variant” more frequently.