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Variant Investigation by Quest (Variant IQTM): Finding Color in a World of Gray Results

You hear them every day. The questions patients ask: What’s causing my symptoms? Why did this happen to me? What are the chances that I might pass this on to my children? The answers aren’t always clear. When it comes to a genetic diagnosis, you want the most reliable, up-to-date, understandable information.

We understand your challenge. We understand your quest for insight. That’s why we’ve developed a team and a process for determining the significance of genetic variants.

We understand your goals, and we work with you. Our high-touch approach optimizes the value of modern science and human insight. We look for color in a world of gray results.

The Team: Variant IQTM and Athena InsightTM

Variant IQ™ and Athena Insight™, Variant IQ’s Neurology Division, are a team of highly specialized and rigorously trained scientists and genetic counselors, whose primary focus is to assess the pathogenicity of genetic variants identified in patients. We strive to provide the best service for our customers by staying up-to-date with relevant literature and diagnostic tools. We stay current with medical science by attending conferences, presenting research, and sustaining collaborations, such as participation in ClinGen Working Groups and partnerships with academia.

The Process

To assess the pathogenicity of genetic variants in patients, we use a rules-based, weighted process (published by our group in 2015) that is aligned with the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines. We conduct a thorough investigation of published research, which is then integrated with data from our internal dataset, external databases, research collaborations, and clinician-provided phenotypes. Close collaboration among our scientists, genetic counselors, and clinical laboratory directors ensures that all the relevant information has been collected and systematically analyzed in order to provide the most clinically informative result to our clients.

Family Insight Program

Within our Variant IQ program, our Family Insight Program looks to determine whether a variant of unknown significance (VUS) is tracking with the disease in the family.

When a variant’s contribution to disease is uncertain and cannot be identified as either benign or pathogenic, the genetic variant is reported as a VUS. When this occurs, Quest Diagnostics performs an in-depth investigation to evaluate the likelihood that the VUS causes disease. The details of this investigation are included in your clinical result report.

We use numerous methods and techniques to gather information about VUS. One of these tools is the Family Insight Program, which allows for segregation analysis, or determining whether the VUS is tracking with the disease in the family. By gathering clinical and family history information on your patient, we are able to identify appropriate family members to offer testing for the VUS identified in your patient. We offer this program with the hope of further elucidating the significance of the variant(s).

It is important to note, participation in the Family Insight Program does not guarantee VUS reclassification. Participation of family members in the Family Insight Program should also not replace genetic counseling and/or clinically indicated genetic testing.

Additionally, incidental findings identified through this program will not be evaluated. Identity testing may be performed as a quality measure. There is no additional charge to family members tested under this program. However, individuals will not receive a report, nor will they learn their genetic testing results. At the completion of the program, your patient’s report may be updated to incorporate any additional information we were able to glean about the variant interpretation for your patient.

If the VUS is reclassified as part of the Family Insight Program, we will contact you.

If the VUS is not reclassified as a result of the family testing, it is possible new information (external and internal) will become available in the future that may cause the VUS classification to change. Since we cannot predict if or when this reclassification will occur, it is important for your patient to remain in contact with your office to ensure they can also be notified of any change in the interpretation of the VUS.

We will not offer testing to family members if:

  1. The variant has been classified as benign, likely benign, likely pathogenic, or pathogenic or if the patient has an otherwise positive report.
  2. The VUS is associated with a specific inheritance pattern and further family genetic information will not clarify the significance of the VUS.
  3. Phenotype of the patient is inconsistent with the reported phenotype of the gene(s) involved.

If your patient is interested in participating in our Family Insight Program, please access the Family Insight Program Application and Consent forms.

Upon receipt of completed information, we will notify you about whether or not your patient has been approved for the Family Insight Program.

If you want an update on the classification of a variant, please fill out a Variant Update Request here.

Action and Education

To request an update on the classification of a variant, please use the form below.

To learn about the Family Insight Program and to contact our genetic counselors, please click here:

To learn more about our group’s research please refer to our publications and conference presentations:

Only a patient’s treating physician can make diagnoses, prognostic or treatment decisions based on the knowledge of the patient, history and clinical/educational experience. Quest lab testing provides information for the physician to use in helping make such decisions.

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