If you are a BRCA mutation carrier, the specific location of your mutation is provided in your genetic test report. At this time, the BRCAlive Tool only applies to known deleterious mutations – those known to increase cancer risk. If your mutation is a variant of unknown significance (VUS), we do not have enough information to conclude whether the mutation increases cancer risk or is completely benign. As more patients share their genetic information via data exchanges, however, we hope to better understand VUS mutations, and eventually classify them as deleterious or benign.
There are multiple genetic naming conventions, which can be somewhat confusing. One of the most common naming systems is called HGVS Nucleotide, which is what the BRCAlive Tool uses. Some testing companies (including Color Genomics) report HGVS, while others (like Myriad) may use an older nomenclature called BIC Designation. Fortunately, it is easy to switch between the two as illustrated below.
Example: Suppose Jane Doe receives the following genetic test results from Color Genomics. The test indicates that Jane carries a BRCA1 mutation located at c.3178, where there is a nucleotide substitution: a guanine (G) nucleotide instead of thymine (T). Your report might instead indicate that a nucleotide has been deleted (del) or inserted (ins), and the letters could also be adenine (A) or cytosine (C). For the BRCAlive Tool, we only focus on the mutation location (c.3178), not the specific nucleotides (A, C, T, G).
A similar report from Myriad is shown below. Here, Jane’s BRCA1 mutation is E1060X (3297G>T). Note there is no c. before 3297, which tells us this is not the HGVS Nucleotide naming system.
However, we can easily search for it using the publicly available BRCA Exchange database.
If we search for E1060X, we can obtain more information about this particular variant, including the HGVS Nucleotide name: c.3178G>T.
For the BRCAlive Tool, first select Mutation Type (BRCA1 or BRCA). Next, from the Mutation Location drop-down menu, select the range of values that your specific mutation falls into. In our example, Jane’s mutation location is c.3178 so the correct bin is c.3014-c.3254.
In the tool, the three Ashkenazi Jewish founder mutations are also clearly labelled.