Although much has been learned about DNA and the human genome over the last several decades, there remains significant knowledge to be gained.  As such, patients may receive results indicating a variant of uncertain significance or VUS, meaning although a variant is present, adequate information is not available to determine the possible implications, if any, to the patient’s health. 

Patients who receive a VUS result are often unsure of what to do next.  One option is to conduct Family Segregation Studies (FSS) which may be helpful in assessing the clinical significance of a patient’s VUS test result.  FSS is an evaluation of specific relatives to determine if they have the same VUS result as seen in the initial patient.  The results may assist the laboratory in reclassification of the variant from a VUS to another classification. Integrated Genetics reports VUS results in three categories: VUS Possibly Benign, VUS, and VUS Possibly Pathogenic. A patient who receives test results from Integrated Genetics with any category of VUS may be considered for FSS. The table below reviews the possible results types with their definitions.

Determining VUS significance with Family Segregation Studies
Result Definition
VUS – variant of uncertain significance Unclear if the change causes or will pose an increased risk to develop the specified condition
VUS, possibly pathogenic Uncertain if the change causes or will pose an increased risk, but a small amount of data suggests the variant may be associated with the specified condition
VUS, possibly benign Uncertain if the change causes or will pose an increased risk, but a small amount of data suggests the variant may not be associated with the specified condition

Healthcare providers may request FSS by calling Genetic Services Client Service at 1-800-345-GENE (4363). Clients will be asked to submit a family pedigree, relevant personal and family clinical history, and information about the availability of family members who are interested in testing. A laboratory director will review the request and provide documentation to determine if FSS studies are likely to aid in the reclassification of the VUS.  For additional information on Family Segregation Studies, please contact Genetic Services Client Service at 1-800-345-GENE (4363).