Family Studies Program

Ambry Genetics makes every effort to help clarify clinical implications of variants of unknown significance (VUS) via co-segregation analysis through its Family Studies Program

Accurate classification of a VUS 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. Follow-up 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 study include: cancer genetics, genes linked to intellectual disabilities and results from other next generation sequencing 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 approval for testing.

Of note, segregation analysis via the Family Studies Program does not guarantee VUS reclassification. Classification of variants is based on multiple lines of evidence, with segregation analysis representing one of these lines of evidence. Furthermore, not all family members are informative for follow-up testing, and additional details or documentation of a family member’s clinical findings may be requested.

Benefits of performing family studies for VUS classification include assessing if an alteration is an inherited or de novo event and determining segregation with disease. These factors in turn aid in assessment and interpretation of an alteration’s pathogenicity.

Exclusion criteria for family study are:

  • Genetic alterations with a classification other than VUS*
  • High frequency of the variant in the general population, or in the 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
    *VLPs may be considered for family study on a case by case basis

Family Studies Process:

  • Download and complete the appropriate Family Studies Application (see below)
  • Please include detailed pedigree and any available clinical notes
  • Ambry’s Family Studies team will notify you once the application is received and reviewed (in 7-10 business days)
  • Results are summarized in a family study report for the proband, complete with interpretation by our clinical staff. In certain cases, we may elect to initiate variant testing after all approved familial specimens are received.
  • Please direct questions to

*Application and required materials can be faxed to Ambry Genetics at 949-271-5621 ATTN: Family Studies

Turnaround time: 4-6 months

Additional Information

Additional Forms: