Cardiology

Cardiology Variant Testing Program (VTP)

Laboratories classify genetic changes as variants of uncertain significance (VUS) if there is insufficient 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 either a positive or negative result.

We consider requests for the Cardiology Variant Testing Program (VTP) for any individual found to have a VUS through testing at our laboratory. There is no charge for targeted variant testing for approved family members.

Which family members may be eligible for the VTP:

  • Up to two affected family members may be approved to assess segregation.
  • If the family history is negative, both parents may be approved to assess de novo status.

Required documentation for consideration for the VTP:

  • Clinical records of proband to confirm presentation is consistent with gene-disease association
  • Detailed family history or pedigree
  • Clinical records of family members applying for the VTP (see table below)

 

Gene/Disease Association Minimum Required Documentation
Cardiomyopathy Echocardiogram
Arrhythmia Relevant cardiac evaluation
Thoracic aortic aneurysm/dissection Echocardiogram including aortic root dimension
Heritable disorders of connective tissue Clinical documentation of gene-relevant features
Dyslipidemia Lipid panel
Hereditary hemorrhagic telangiectasia (HHT) Clinical documentation of Curacao criteria

 
Please submit the required documentation to our cardiology genetic counselors via fax (201-421-2010), email (zebras@genedx.com), or call 301-519-2100 and ask to be speak to a cardiology genetic counselor. Please indicate you are submitting the information for cardiology VTP consideration and include the name and/or GeneDx accession number of the proband. Cases are typically reviewed within one week of receipt. After the request has been reviewed, a member of our VTP team will contact the ordering provider to discuss whether and which family members have been approved for the VTP or whether additional information is needed.

Reasons why a family might not be accepted into the Variant Testing Program:

  • The variant is in a gene that does not correspond to the documented presentation in the proband.
  • There are pathogenic or likely pathogenic variant(s) in the family that explain the disease.
  • There are no informative family members available for testing. (i.e. All affected relatives are deceased and/or unavailable, and no postmortem specimens are available.)
  • If both parents are not available in cases with a negative family history, we cannot accept only one parent as this does not aid in determining if a variant occurred de novo.

Reclassification of variants of uncertain significance requires substantial data and information from multiple sources. Therefore, there is no guarantee that participation in the Cardiology Variant Testing Program will lead to reclassification of a VUS.

For more information, please contact the cardiology genetic counselors at 301-519-2100