What is My Variant?
It's important to understand your variant. Your DNA is the code that tells the cells in your body cells what to do. It comes packaged as two copies of 22 different chromosomes inherited from your mom and dad, and either two XX chromosomes or an X and a Y chromosome. Each chromosome is a single string of DNA with many genes. Each gene consists of hundreds or thousands of DNA base pairs, represented by the letters A, C, T, and G. These make the DNA code that spells out how to make a protein. Proteins are the building blocks of your body.
If you have had clinical genetic testing for a disease or strong family history you may have received a report that lists a variant (or mutation) in a gene. Sometimes people only notice the gene listed, like BRCA1 or APC. The gene and variant listed on your report give different levels of information. The part of your report that lists the gene name gives a high-level view of what is not working. The part of your report that lists your specific variant will tell you and your doctor exactly what is wrong with the gene.
Specific variants are usually listed with a number that starts with “c.” and has numbers and letters after. For example, “c.137G>T” is a pathogenic variant in the gene PMS2 that causes Lynch syndrome. The numbers indicate the base pair position in the PMS2 gene (position 137) and the letters indicate the change: G in most people at position137, but T is what was seen on testing. Some reports may also list protein change, which starts with a “p.” followed by letters and numbers. PMS2:c.137G>T is also called “p.Ser46Ile” indicating amino acid 46 in the PMS2 protein is changed from Serine to Isoleucine. Both report the same change, one on the DNA level and the other on the protein level. Sometimes only the “c.” DNA change is there because the protein change is complicated. Sometimes two different DNA changes can cause the same protein change.
If you look at your full genetic report, you should be able to find your specific variant listed. If you cannot find it or are not sure, ask your doctor or genetic counselor for help.
Why Does My Specific Variant Matter?
Talking about which gene that does not work is like saying, “My car is broken.” or “My refrigerator won’t work.” Talking about this situation with others in the same situation can be extremely helpful; you can learn how to catch the bus or which foods will go bad first. Talking about which variant you have can be even more helpful, because it provides more specific information. Like saying, “The timing belt on my car went out.” or “There was a ton of cat hair blocking my refrigerators condenser coils.” Having this level of information can be even more helpful.
Just like most car problems have the same effect of preventing the car from running, most different variants in the same gene have the same ultimate effect. However, some variants can have slightly different effects or cause different risk levels. It can be hard to figure out differences in risk between variants. Talking with others with your same variant may reveal that your variant is similar to every other variant in the same gene, or it may make you suspect that it is different.
When someone else has the same very rare genetic variant as you, you may share a lot more than the same risk. Almost all mutations happened for the first time with a single person in history. (There are few documented to have happened more than once.) That person could be alive today or could have lived hundreds of years ago. Once a mutation is passed down to a person’s children, grandchildren, and so on, it is usually called a variant rather than a mutation. In common usage, both words “variant” and “mutation” mean almost the same thing. Everyone with your variant is probably related to the same ancestor, so your specific variant is a key to understanding your past. It is also key that you can use to help your relatives prevent disease before it happens.