Neurology

Neurology Variant Testing Program (VTP)

Laboratories classify genetic changes as variants of uncertain significance (VUS) if there is incomplete or conflicting information about the health consequences of the variant. In some cases, testing family members for the presence or absence of the VUS may contribute to a better understanding of the variant and may be one piece of evidence leading to eventual reclassification of a VUS as a pathogenic, likely pathogenic, benign, or likely benign variant. For such cases, GeneDx has established a Variant Testing Program (VTP).

How do I determine if a variant is eligible for the Neurology VTP?

GeneDx considers requests for the Neurology VTP for any individual found to have a VUS identified through Neurology genetic testing at our laboratory. Given the high rate of de novo variants in some neurological disorders, we may also offer the VTP to parents of an individual with a likely pathogenic (LPATH) variant. These studies will be performed at no additional charge for select and pre-approved family members who meet certain criteria and for whom appropriate clinical information is provided. Genetic testing for other variants or additional family members, including predictive testing, is not included in our VTP and can be ordered separately for charge. GeneDx will make the final determinations for VTP in its sole discretion.

Application process for the Neurology VTP:

  • In some cases, the ‘Recommendations’ section of the proband’s report may specify that testing for a VUS is available at no additional charge through the VTP for the biological mother and biological father of the proband. Clinical information on the parents (and proband) must be provided at the time of testing in order for targeted testing to be performed at no charge, but no additional prior approval is required for these cases.
  • If parents are not available, there may be other informative family members eligible for VTP testing. Requests to consider testing for relatives other than the biological parents, or requests for other variants not specified in the ‘Recommendations’ section of the report, should be submitted for advance review. Please fax a detailed pedigree and any relevant clinical information/evaluations to the GeneDx Neurology genetic counselors at 301-519-2892, email zebras@genedx.com, or call 301-519-2100 and ask to speak with a Neurology genetic counselor. Please be sure to indicate that you are submitting the information for VTP consideration and include the name and/or GeneDx accession number of the proband.
  • Our team will review the case and will determine if there are informative family members appropriate for evaluation through the VTP. Cases are typically reviewed within a few days, but please allow up to 3 weeks after receipt of the application for a reply.
  • A member of our team will contact the ordering provider or genetic counselor after the case has been reviewed to let him/her know if the family has been accepted in the VTP. If we are extending an offer for family member variant testing at no additional charge, we will discuss logistics of sample submission at that time.
  • Our typical policy is that we will test up to two informative family members at no charge. On a case by case basis, we may consider testing additional family members at no additional charge, depending on the disorder and the family history.

Reasons why a family might not be accepted into the Neurology VTP:

  • There are no informative family members available for testing.
  • In certain circumstances, it may be more informative to perform more comprehensive diagnostic genetic testing in affected family member(s) instead of targeted testing of one or more unaffected relatives for a VUS.
  • The VUS is in a gene for which there is no currently described phenotype (i.e. candidate or novel gene).
  • The variant is in a gene that does not correspond well with the clinical phenotype reported in the proband or the medical history in the family.
  • Segregation studies involving genes with incomplete penetrance or variable age-of-onset are challenging, especially in unaffected individuals; therefore, VTP studies are less likely to be approved for such genes.
  • Segregation studies involving genes that may cause either an autosomal dominant or an autosomal recessive disorder are also more challenging than studies involving highly penetrant autosomal dominant genes; therefore, VTP studies are less likely to be approved for such genes.
  • Variant studies for the evaluation of a single VUS in a gene associated with an autosomal recessive disorder are rarely informative. Therefore, these requests are typically denied.

Revising the classification of variants of uncertain significance takes a great deal of data and information from multiple sources. Therefore, there is no guarantee that participation in the VTP will lead to an updated classification of a VUS based on information from a single family, although cumulative data collected from multiple families over time may lead to a more definitive classification for a variant.

For more information please contact:
The GeneDx Neurology Genetic Counselors at 301-591-2100