VUS Clarification

Blueprint Genetics is dedicated to advancing and improving the field of genetic diagnostics. In addition to our philosophy of transparency and public variant sharing in ClinVar, we offer a Variant of Uncertain Significance (VUS) Clarification Service. This is a free follow-up testing program for family members of patients tested at Blueprint Genetics. The goal of the service is to gain evidence in order to re-classify the identified VUS, either likely benign/benign or likely pathogenic/pathogenic.

Re-classification of the variant will lead to an amended report that will be sent to all the individuals who tested positive for the variant. We will also update our interpretation and classification in public databases such as ClinVar and ultimately help other patients and families who have tested positive for the identified variant.

Who qualifies for the service?

Not all variants and cases qualify for the VUS Clarification service. Furthermore, not all family members are informative for the required level of evidence. It is important to understand whether or not the family members to be tested will provide the information necessary for reclassification. The following characteristics will influence qualification for this service:

Family history:

  • Positive family history: Influencing factors are the number of affected family members (at least 3) and the clinical presentation of individuals in the family.
  • Negative family history: Typically cases with a clear syndrome or disorder that is mainly caused by a de novo mutation or inherited from a mosaic parent, or disorders with recessive inheritance. In these cases, testing of only parents can be considered.

Genotype-Phenotype association:

In all cases, we require a strong association between the gene and patient’s phenotype. Not all genes in Blueprint Genetics platforms necessarily fulfill criteria for this service. Typically, appropriate genes are well-established disease genes and harbor mutations that can be classified as pathogenic.

Mode of inheritance: The inheritance pattern is logical in the context of disease, gene and the suggested testing strategy.

How do I apply?

The application form is available here. Blueprint Genetics ID of the original patient (index) tested at Blueprint Genetics is critical information. We also request to describe the variant in question proposed for testing . Detailed family history and the description of clinical phenotypes of all affected family members is critical (see above criteria recommendations). Application documents should be sent to us via mail or by fax. If you contact our customer support via email, please do not include any medical records or medical information with your initial inquiry.

Apply here