In certain circumstances, family members of individuals tested at Fulgent may be eligible for complimentary, no-cost Familial Known Mutation Testing. This page outlines our eligibility requirements and best practices to help ensure clinically useful results.
What is Familial Known Mutation Testing and why is it performed?
Occasionally, individuals may receive a genetic testing report with an uncertain result, called a "variant of uncertain significance" ("VUS"). When this occurs, it can be useful to test additional family members in order to evaluate if they have the same VUS. This type of genetic segregation testing helps identify if the VUS tracks with a known condition in the family.
This type of test is generally called "familial known mutation testing." It is a targeted test, intended to look for a specific VUS in biological parents. This testing is performed when such analysis may provide informative and meaningful insight into the variant's classification and has the potential to change clinical management.
This includes situations where a test report has two variants in an autosomal recessive gene. For autosomal recessive genes, a likely pathogenic or pathogenic (disease causing) variant needs to be present on both copies of the gene in order to be affected. If an individual has one pathogenic variant and one VUS, it can be very useful to test the biological parents to identify the inheritance of this variant (phasing) and apply additional ACMG variant interpretation criteria to aid in variant reclassification. In other inheritance scenarios in which only one pathogenic variant needs to be present in order to be affected (e.g. X-linked or autosomal dominant conditions), reclassification can also be aided by segregation analysis. Determining whether the VUS is found in a similarly affected biological parent or occurs "de novo" (i.e. was not inherited from either biological parent) can assist with variant classification per ACMG criteria.
