Accurate classification of VUSs is integral to understanding the ramifications of genetic results for many patients and their families. However, such classification is often a challenge due to conflicting or limited available information. Complimentary testing of appropriate family members through Ambry’s Family Studies Program can provide additional, powerful information to aide in VUS classification.

Primary areas of VUS research include: cancer genetics, genes linked to intellectual disabilities and results from cardiac panels. The Family Studies Program operates on a case-by-case basis: requiring a review of the patient’s family history and clinical findings by our clinical diagnostics team prior to complimentary testing approval.

Of note, segregation analysis via the Family Studies Program does not guarantee VUS reclassification. Furthermore, not all family members are informative for complimentary testing, and additional details or documentation of a family member’s clinical findings may be requested.

Benefits of performing family studies for VUSs include:

• Elucidating if the genetic change is inherited or a de novo event
• Helping to understand disease segregation
• Determining associated co-morbidities
• Predicting recurrence risk and risk to first-degree relatives

Exclusion criteria for complimentary testing are as follows: 

• Genetic alterations with a classification other than “VUS”
• High frequency of the variant in the general population or specific cohort
• Discordance between the proband’s clinical symptoms and documented phenotypes associated with the gene of interest
• Lack of informative family members available for testing

Family Studies Process:

• Download and complete Family Studies Application*
• Please include detailed pedigree and clinical notes
• Ambry’s Clinical Diagnostics team will notify you once application is received and reviewed (in 7-10 business days)
• Complimentary testing is initiated after all approved familial specimens are received (must be within 6 months from time of approval)
• Results are summarized in a laboratory report complete with interpretation by our clinical staff
• Please direct questions to CancerGC@ambrygen.com, XLID@ambrygen.com or GeneticCounselor@ambrygen.com

*Application and required materials can be faxed to Ambry Genetics at 949-900-5501 ATTN: Genetic Counselor.

Turnaround time: 4-6 months (or longer) after receipt of last approved familial specimen

Additional Forms:

• PCD Application for Family Studies
• Marfan Application for Family Studies
• Cancer Application for Family Studies
• XLID Application for Family Studies
• VUS Patient Brochure