Targeted variant testing
Targeted genetic testing for known familial variants
When genetic testing identifies variants in a patient, targeted variant testing may be indicated for family members. Targeted variant testing is less costly than diagnostic analysis of the whole gene or panel of genes.
What is targeted genetic testing?
Targeted genetic testing analyzes a specific, previously identified genetic variant in a patient or family member. It is commonly used for cascade testing, carrier testing, confirmatory testing, and mosaic variant analysis.
How targeted variant testing supports care
We offer a comprehensive menu of targeted variant testing options to meet the needs of families and healthcare providers. Targeted variant testing is often ordered by healthcare providers in the following situations:
- Diagnostic or predictive testing for a patient’s at-risk family members after pathogenic or likely pathogenic variant(s) are identified by genetic testing of an affected patient.
- Carrier testing to assess reproductive risk for people who may be carriers of a familial genetic disorder.
- Segregation analysis to help clarify the clinical significance of a variant of uncertain significance (VUS). If the VUS was identified through genetic testing at GeneDx, eligible family members may receive targeted variant testing at no additional charge.
- CLIA-approved laboratory confirmation of variant(s) previously identified in a research setting.
- Mosaicism testing for a specific variant previously identified in a different tissue in an affected patient or in a family member.
Targeted genetic testing options for family members and providers
Review the test options below for more information about the specific services we provide.
Familial Risk Assessment
Once a pathogenic or likely pathogenic variant is identified in the proband, targeted testing of family members may be indicated to evaluate their risk. We strongly recommend submission of a positive control specimen from a relative who tested positive for any targeted testing if one is not already available at GeneDx. In some cases, a positive control may be required to proceed with testing.
- Targeted testing is less costly and more rapid than diagnostic analysis of the whole gene or panel of genes and will provide either a “negative” or “positive” result.
- GeneDx offers targeted testing for families whether they have had previous testing at GeneDx or another laboratory.
- Targeted testing for the familial variant(s) is available in any gene for both symptomatic and asymptomatic individuals, and for autosomal dominant and recessive, X-linked or maternally inherited mitochondrial variants.
- The ordering provider will need to provide information on the proband’s previous testing results, including the gene(s) and variant(s), when ordering (see links to the left for details).
- To order targeted testing for family members:
- Print out a GeneDx test requisition form or click here for online ordering.
- Select the desired test from the ‘Targeted Variant Testing’ section.
- Provide information on the proband’s previous testing results, including the gene(s) and variant(s) that need to be tested.
Variant of uncertain significance (VUS) segregation analysis. When a variant of uncertain significance (VUS) is identified in the proband, testing family members may provide more information about the potential pathogenicity of the variant.
- GeneDx offers targeted testing for families whether they have had previous testing at GeneDx or another laboratory.
- Targeted testing for a VUS is available for most genes for both symptomatic and asymptomatic individuals, and for autosomal dominant and recessive, X-linked or maternally inherited mitochondrial variants.
- The ordering provider will need to provide information on the proband’s previous testing results, including the gene(s) and variant(s), when ordering (see links to the left for details).
- To order targeted testing for family members:
- Print out a GeneDx test requisition form or click here for online ordering.
- Select the desired test from the ‘Targeted Variant Testing’ section.
- Provide information on the proband’s previous testing results, including the gene(s) and variant(s) that need to be tested.
- If the VUS was identified through testing at GeneDx, family members may be eligible for targeted testing at no additional charge through the Variant Testing Program. Click here for more information.
What information do I need to provide to order targeted variant testing on an individual when their family member was tested at GeneDx?
- If available, please submit the GeneDx laboratory report on the family member.
- Please list the variant and provide the family member’s specimen ID/name/date of birth.
For Nuclear Gene Variants:
- The name of the gene.
- The variant in cDNA-level notation (e.g. residue c.123 G to T, where c.1 is the A of the initiator ATG).
- One of the following:
1. The variant given in protein-level notation (e.g. Gly12Ser or G12S).
2. The variant given in gDNA-level notation, with reference to a specific public reference sequence.
3. A DNA sequence at least 30 bases long with the altered base and variant indicated.
For Mitochondrial (mtDNA) Variants:
- The name of the gene.
- The position in the mitogenome (m.) using reference sequence NC_012920.
How do I order targeted variant testing on an individual when their family member was tested at GeneDx?
- Use a GeneDx Test Requisition Form or order online.
- Select Targeted Variant Testing and Special Services (all other requisitions).
- Provide the name of the gene and name of the variant (using the format above).
- Enclose a copy of the GeneDx report on the family member, if available.
- For mitochondrial DNA (mtDNA) variants, select one of the Known mtDNA Variant(s) test options.
- Please refer to our specimen requirements page prior to submitting a specimen.
What is the turn-around time?
- Test results are generally available in 2-3 weeks*.
- Written report(s) are sent to the ordering healthcare provider.
* Reporting times are typical estimates, but could be extended in situations outside GeneDx’s reasonable control.
GeneDx can provide targeted variant testing to family members when testing was originally performed by another, non-GeneDx laboratory. We recommend submitting a specimen from a relative with the variant(s) of interest as a positive control, but this is not required in all cases.
What information do I need to provide to order targeted variant testing on an individual when their family member was tested at another diagnostic laboratory?
- If available, please submit the outside molecular diagnostics laboratory report on the family member.
Please identify the variant:
For Nuclear Gene Variants:
- The name of the gene.
- The variant in cDNA-level notation (e.g. residue c.123 G to T, where c.1 is the A of the initiator ATG).
- One of the following:
1. The variant given in protein-level notation (e.g. Gly12Ser or G12S).
2. The variant given in gDNA-level notation, with reference to a specific public reference sequence.
3. A DNA sequence at least 30 bases long with the altered base and variant indicated.
For Mitochondrial (mtDNA) Variants:
- The name of the gene.
- The position in the mitogenome (m.) using reference sequence NC_012920.
For Copy Number Variants (CNVs):
- Email support@genedx.com to confirm availability and gene coverage.
For single gene or intragenic CNVs:
- The name of the gene.
- The exons involved and transcript number OR genome build and genomic coordinates.
For multigenic CNVs:
- The genome build and genomic coordinates.
- For GeneDx portal orders, select a gene from within the genomic region from the list. If you do not know or cannot find any genes within the region, select “XYZ” from the list as a placeholder.
How do I order targeted variant testing for an individual when their family member was tested at another diagnostic laboratory?
- Use a GeneDx Test Requisition Form or order online.
- Provide the name of the gene and name of the variant (using the format above).
- Enclose a copy of the outside diagnostics laboratory report, if available.
- For mitochondrial DNA (mtDNA) variants, select one of the Known mtDNA Variant(s) test options.
- Please refer to our Specimen Requirements page prior to submitting a specimen.
Is a positive control required?
- No, a positive control is not required*. However, including one is beneficial, and we strongly recommend submission of a positive control specimen for any targeted testing, if one is not already available at GeneDx. In some cases, a positive control may be required to proceed with testing.
- Without a positive control, we may not be able to confirm that a negative result is truly negative.
- Please complete the Family Member Test Requisition Form with the information of the relative who will be sending a specimen as the positive control. The completed form can be sent back with the buccal kit for this relative OR it can be uploaded to the portal documents for your patient’s targeted test order. THere is no additional charge to submit a positive control and this relative will not get their own report.
- If requested, a report for the positive control family member is available for an additional fee.
- Please call one of our genetic counselors if you would like to discuss the submission of a positive control.
*A positive control is not needed for mtDNA variants.
What is the turn-around time?
- Results are generally available in 2-3 weeks*.
- Written report(s) are sent to the ordering healthcare provider.
*Reporting times are typical, but could be extended in situations outside GeneDx’s reasonable control.
We can analyze almost any gene to confirm a variant that has been identified in a research laboratory. Unlike most research laboratories, GeneDx is a CLIA-certified clinical service laboratory and can release results of testing to referring healthcare providers for use in diagnosis, counseling, and development of a treatment plan.
Guidelines:
- Must be ordered by a healthcare provider.
- A new specimen (usually blood or buccal swab) from the individual is required to confirm that the variant is present.
- This confirmation of the variant in the previously-tested individual is necessary before we can perform targeted variant testing or prenatal diagnosis in the family.
What information do I need to provide to order a variant confirmation test?
Please provide variant information to GeneDx prior to sending in the specimen(s). This information may be in the form of a publication, lab report, or other communication from the laboratory, in which the variant was previously observed.
To clearly identify the variant, please provide:
For nuclear gene variants:
- The name of the gene.
- The variant in cDNA-level notation (e.g. residue c.123 G to T, where c.1 is the A of the initiator ATG).
- One of the following:
- The mutation variant given in protein-level notation (e.g. Gly12Ser or G12S).
- The mutation variant given in gDNA-level notation, with reference to a specific public reference sequence.
- A DNA sequence at least 30 bases long with the mutated altered base and mutation variant indicated.
For mitochondrial (mtDNA) variants:
- The name of the gene.
- The position in the mitogenome (m.) using reference sequence NC_012920.
How do I order variant confirmation?
- Use a GeneDx test requisition form. This test can be found in the Targeted Variant Testing section located after the main test list on all requisition forms.
- OR Order Online by selecting the appropriate targeted test and indicate “Research confirmation” in the comments section.
- Provide the name of the gene and name of the variant (using the format above).
- Enclose a copy of the research report, if available.
- For mitochondrial DNA (mtDNA) variants, select one of the Known mtDNA Variant(s) test options.
- Please refer to our specimen requirements page prior to submitting a specimen.
What is the turn-around time?
- Test results are generally available in 3-4 weeks*.
- Written report(s) are sent to the ordering healthcare provider.
* Reporting times are estimates, but could be extended in situations outside GeneDx’s control.
Targeted testing to evaluate for mosaicism for a variant previously identified in an individual or family member.
GeneDx offers targeted testing to evaluate for mosaicism for a familial variant previously identified in an individual or in a family member. Targeted Mosaic Variant Testing could be considered in the following scenarios:
- Testing parent(s) to clarify future reproductive risks when a variant was identified in a child.
- Testing a parent who is suspected to be mosaic due to a mild clinical presentation or the presence of only certain tissue-specific features of the disorder.
- Testing additional tissue specimens to evaluate for the possibility of tissue-specific mosaicism in a proband.
- CLIA confirmation of suspected mosaic findings identified by a research study.
Targeted Mosaic Variant Testing is available for many variants in genes on the GeneDx testing menu. In many cases, Targeted Mosaic Variant Testing is also available for individuals who had variants identified by testing at an outside laboratory or as part of a research study. If the family has not had prior testing at GeneDx, please see the table below for the specific requirements. At this time, Targeted Mosaic Variant Testing is not available for copy number variants (CNVs). Additionally, there are some genes or portions of genes that are not amenable to Targeted Mosaic Variant Testing for sequencing variants. If prior trio testing was performed including the patient and both parents as part of exome or genome sequencing, an Xpanded panel, or another testing scenario, please contact GeneDx in advance of specimen submission to discuss the utility of Targeted Mosaic Variant Testing.
| Scenarios when mosaic carrier analysis could be considered: | Specimen from Patient as Positive Control | Copy of Report from Non-GeneDx Laboratory | Preferred Specimen Type |
|---|---|---|---|
| 1. Evaluate for parental mosaicism when proband not tested or tested by Sanger sequencing: Parents not tested or tested by Sanger sequencing. | Not Necessary | Not Necessary | Blood or Buccal swab |
| 2. Evaluate for parental mosaicism when proband tested by research study or at outside lab: Parents not tested or tested by Sanger Sequencing | Required | Required | Blood or Buccal Swab |
| 3. Evaluate for mosaicism in an affected parent: Parent had prior testing as part of trio testing for proband that was negative for the variant. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Please call in advance to discuss. |
| 4. Evaluate for parental mosaicism when there are multiple affected children: Parent had prior testing as part of trio testing for proband that was negative for the variant. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Please call in advance to discuss. |
| 5. Evaluate for suspected mosaicism in proband previously reported to be heterozygous for variant: Proband reported to be heterozygous for variant by prior testing, but clinical features suggest possible mosaicism. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Please call in advance to discuss. |
| 6. Evaluate proband to differentiate acquired or somatic mosaicism from constitutional variant: Proband is heterozygous or mosaic for variant in DNA extracted from blood. | Not necessary if prior testing is done at GeneDx. | Not necessary if prior testing is done at GeneDx. Required if done at an outside laboratory. | Skin punch biopsy is recommended |
To order targeted mosaic variant testing, please use this requisition form, and provide the requested information:
- The name of the gene.
- The specific variant for mosaic targeted testing.
- If the patient or a family member was previously tested at GeneDx, provide the GeneDx accession number and/or the full name of the relative.
Please see our standard specimen requirements page for obtaining and shipping specimens. The requisition form MUST accompany the specimen or testing may be cancelled or delayed.
Turnaround times for targeted variant testing
These timelines reflect the typical reporting windows for targeted variant testing, variant confirmation, and mosaic evaluations.
Weeks
For targeted variant testing
Weeks
For variant confirmation / mosaic testing.
