When testing a gene, many different types of genetic changes are identified. Some genetic changes clearly impair the function of the gene (that is, they are pathogenic) and may cause disease. Other genetic changes are benign – causing no problems with the gene and creating no medical problems for the individual.
However, some genetic changes are not easily classified as either pathogenic or benign. These genetic changes are called unclassified variants. Unclassified variants present a dilemma for researchers, clinicians, and patients – all of whom are seeking clear, informative genetic test results. When an unclassified variant is identified in a patient’s genetic test results, it is unknown whether or not that variant has caused or could cause disease in the patient (or his/her family members).
Many researchers are working to gain more information about variants to definitively classify them as benign or pathogenic. However, this research takes time. Until a variant can be classified, care for patients and their relatives is typically planned using what is definitely known – with tailored treatment and screening recommendations based on the patient’s personal and family history rather than the genetic variant.
Researchers at Huntsman Cancer Institute at the University of Utah (HCI) have been involved with unclassified variant research for many years. Their research has focused on classifying variants in genes associated with hereditary cancer risk, including BRCA1 and BRCA2 and the mismatch repair genes. To increase access to genetic variant information, we have created this portal. By following the links below, you can access multiple internal and external databases full of information on variants in genes associated with hereditary cancer. You can also review Powerpoint slides, videos, and articles on the topic of genetic variants. These databases are updated frequently, so we encourage you to check back regularly.
If you have questions on genetic variant research, please contact Sean.Tavtigian@hci.utah.edu.
If you or one of your patients has received a genetic test result containing an unclassified variant and you are looking for additional clinical guidance, please contact the Family Cancer Assessment Clinic at HCI at 801-587-9555. One of the genetic counselors can assist you.
|HCI BRCA1/2 Classified Variant Database||BRCA1/2||hci-exlovd.hci.utah.edu||Curated published data on variants|
|HCI BRCA1/2 Prior Probabilities Database||BRCA1/2||http://priors.hci.utah.edu/PRIORS/||Data on all possible single nucleotide substitutions in BRCA1/2|
|HCI MMR: Prior Probabilities and Classified Variants Database||Mismatch repair (MLH1, MSH2, PMS2, MSH6)||hci-lovd.hci.utah.edu/home.php||Data on all possible single nucleotide substitutions in the MMR genes|
External managed sites
|LOVD-For paraganglioma genes (FH, SDHX)||LOVD-For Paraganglioma genes (FH, SDHX)||chromium.liacs.nl/lovd_sdh/home.php||Curated published data on variants|
|IARC TP53||TP53||p53.iarc.fr/||Curated published data on germline and tumor variants|
|InSIGHT||Mismatch Repair/APC/CDH1||www.insight-group.org/variants/database/||Curated published data on germline variants|
|Breast Cancer Information Core||BRCA1/2||research.nhgri.nih.gov/bic/||Database of submitted VUS information from researchers and clinicians, classifications if available|
|Evidence-Based Network for the Interpretation of Germline Alleles (ENIGMA)||Multiple||enigmaconsortium.org/||Submit variants for research|
Clinical resources at Huntsman Cancer Institute
Family Cancer Assessment Clinic (FCAC) - providing clinical genetics evaluations and hereditary cancer risk assessment for patients
Research resources at Huntsman Cancer Institute
Cancer Genetics Study (CGS) - enrolling patients with personal or family histories that suggest increased cancer risk to gain and refine knowledge about hereditary cancer