Flexible follow-up testing

1. An order is eligible for one re-requisition at no additional charge if:

   • The original order was for a diagnostic panel
   • The re-requisition order is placed within 150 days of the original report release

2. For diagnostic panel re-requisition:

   • The genes added must be within the same clinical area as the initial order and were available at the time of the original order
   • Re-requisition is based on a standard Invitae test. Family members tested under Invitae’s family variant testing program are not eligible for re-requisitions at no additional charge.

3. Please note, we are unable to offer re-requisition from:

   • The SMA STAT panel to other neuromuscular panels
   • A panel test to an exome or from an exome to another test
   • A DNA-only panel to a panel that includes RNA testing
   • A panel that includes RNA testing to a DNA-only panel

If you would like to proceed with testing in these cases, please submit a new order and specimen(s).

Sign in to your Invitae account and view your orders and reports.

• Select the order for which you would like to place a re-requisition
• If the order is eligible for a re-requisition, you will see an option on the order status page to “Add re-requisition”
• Select the content that you would like to order
• Authorize with your initials and click “Submit”

For diagnostic panels, you have the option to specify your re-requisition request at the time you place your initial order. In the online portal or the paper requisition form, you will see an option to reflex to additional tests either when the initial test is negative or regardless of the initial results.

For diagnostic panels, you can order additional genes within another clinical area at any time. These orders will be billed as a new order and will require a new specimen.

Recent evidence shows that only a small percentage of relatives pursue follow-up testing,^1,2 despite having up to a 50% risk of having the same variant. Reasons for not pursuing testing include lack of knowledge about the potential disease risk, family communication barriers, lack of access to genetics services, and cost of testing.^3,4

Our family variant program is part of our commitment to lowering barriers to genetic testing. We believe that everyone should have access to their genetic information so they can make informed health decisions, such as early action to prevent the onset of disease, more frequent or earlier screenings, or alternate reproductive choices.

Blood relatives of a patient who were found to have:

• A pathogenic, likely pathogenic, low penetrance or increased risk allele found on an Invitae diagnostic, genetic risk panel, or single-gene test (not available for exome testing)
• The family variant testing order is placed within 150 days of the original patient’s test report

Invitae requires a paper requisition for exome-related familial variant testing. Download PDF

To order family variant testing:

1. Sign in to your Invitae account and start an order
2. In the “Browse more tests” section, select the “Family testing” card
3. You will need to provide:
   • The order number ("RQ number") of the proband tested at Invitae
   • Proband’s date of birth
   • Relationship to the proband

If you prefer to place your order on paper, you can download this requisition form.

• This patient FAQ page describes how a genetic diagnosis can affect an entire family and why it’s important for family members to get testing.
• Patients can share letters with their relatives to initiate a conversation about the patient's test results and what the results could mean for family members.
  • Lynch syndrome letter
  • HBOC letter
  • General positive letter
• Relatives can bring this letter to their doctor to initiate family variant testing. For Spanish, click here.
• Invitae’s genetic counselors can answer patients’ questions about genetic testing.

Providers should reach out to our Client Services team at 800-436-3037 if they would like to confirm whether a VUS on a patient's report will qualify for no-charge family follow-up testing for a VUS finding. When that’s the case, testing for up to two family members has been pre-approved. Guidance on which relatives will be the most useful for testing can be found in the reference table above (under “Who is eligible?”) or by contacting Invitae’s Client Services team.**

To order VUS resolution testing:

1. Sign in to your Invitae account and start an order
2. In the “Browse more tests” section, select the “Family testing” card
3. You will need to provide:
   • The order number "RQ number" of the original patient (proband) tested at Invitae
   • Proband date of birth
   • Family history and/or pedigree
   • Any medical records that may support the patient’s or family member’s diagnosis, such as clinic notes, pathology reports, and lab results

If relevant medical records are not included, reclassification of a variant will be unlikely. A patient’s clinical features are used to aid in variant reclassification. (See “What else should I include when placing my order?” below for more information.)

Please contact our Client Services team if you have any questions regarding initiating VUS resolution orders or required documentation for your case.

For oncology VUS resolution requests: Please submit a family pedigree indicating the type of cancer and age at diagnosis (when available) for affected relatives. In addition, pathology reports and clinical notes detailing the patient and/or affected family members’ pertinent medical history can be highly useful.

For cardiology VUS resolution requests: Please submit clinical notes summarizing and documenting the patient and/or affected family members’ diagnosis. When applicable, reports containing LDL-C and total cholesterol results, ECGs, exercise stress test result, echo/cardiac MRI interpretation, EP studies, and cardiac biopsy results can be highly useful.

For neurology VUS resolution requests: Please submit clinical notes summarizing and documenting the patient and/or affected family members’ diagnosis, in addition to a family pedigree. When applicable, clinic notes summarizing nerve conduction velocity/EMG results, serum CK, and muscle biopsy testing can be highly useful. For neurodegenerative disorders, fMRI and PET scan results can also be highly useful.

For pediatric VUS resolution requests (including adult-onset disorders): Please submit clinic notes summarizing and documenting the patient’s clinical features, including the age of onset and a detailed summary of the presenting phenotype. In addition, please provide a family pedigree. When applicable, a summary of EEG, MRI, ultrasound, and/or X-ray results can be highly useful.

For immunology VUS resolution requests: Please submit relevant laboratory results, including flow cytometry testing that may be supportive of the patient’s diagnosis, in addition to documentation of the patient’s phenotype and family history.

For metabolic VUS resolution requests: Please submit biochemical testing results, such as analyte testing or enzyme analysis that may be supportive of the patient's diagnosis, in addition to the requested clinical information and family pedigree.

Relatives can bring this letter to their doctor to initiate VUS resolution testing. For Spanish, click here.

Providers should reach out to our Client Services team at 800-436-3037 if they would like to confirm whether a VUS on a patient's report will qualify for no-charge family follow-up testing for a VUS finding.

The report will be labeled with one of the following statuses based on currently available evidence for the variant:

• Recommended: Testing additional family member(s) has a reasonably high likelihood of resulting in a reclassification at some point.
• Not offered: Testing additional family member(s) is unlikely to provide further evidence to result in reclassification. Common examples of VUS in this category include:
  • A single VUS observed in a gene associated with an autosomal recessive condition
  • A VUS observed in an unaffected patient
  • A VUS observed in a preliminary-evidence gene (i.e., genes where currently there is only early evidence of a relationship between variants in these genes and specific diseases)
  • A VUS with population minor allele frequency that is greater than expected to cause disease
  • A VUS that is suspected to be mosaic in the patient

Individuals who don’t qualify for VUS resolution

If VUS resolution is not offered for a patient’s variant, testing additional family members is unlikely to contribute to a reclassification in this family. If you still wish to proceed with testing family members, you are welcome to place a new order for each family member using Invitae's billing options.

Determining which relatives to test when a VUS qualifies for VUS resolution (reference chart below)

When a variant qualifies for VUS resolution, the table below can be used as a guide to help you and the family decide which family members would be the most informative to test. However, this may vary depending on the specific case, and the decision on which family members to test is up to your discretion. Please note that clearly delineating when a relative is affected versus unaffected is crucial in helping Invitae reclassify the VUS. Affected relatives undergoing VUS resolution must be accompanied by a detailed clinical history or clinic note.*