GTR Test Accession:
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GTR000568029.2
Last updated in GTR:
2024-02-07
View version history
GTR000568029.2,
last updated:
2024-02-07
GTR000568029.1,
registered in GTR:
2023-02-08
Last annual review date for the lab: 2024-02-07
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At a Glance
Test purpose:
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Diagnosis;
Mutation Confirmation;
Risk Assessment; ...
Conditions (19):
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Autosomal dominant cerebellar ataxia, deafness and narcolepsy;
ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder;
Alpha thalassemia-X-linked intellectual disability syndrome
more...
Analytes (1):
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Methylation Status
Methods (1):
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Molecular Genetics - Methylation analysis: Microarray
Target population: Help
Abnormalties detected using this initial screen may require additional targeted …
Clinical validity:
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Not provided
Clinical utility:
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Establish or confirm diagnosis
Ordering Information
Offered by:
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Test short name:
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EPISign
Specimen Source:
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- Amniocytes
- Amniotic fluid
- Bone marrow
- Cell culture
- Cell-free DNA
- Fibroblasts
- Fresh tissue
- Frozen tissue
- Isolated DNA
- Paraffin block
- Peripheral (whole) blood
- Urine
- White blood cell prep
Who can order: Help
- Health Care Provider
Test Order Code:
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https://www.lhsc.on.ca/palm/docs/EpiSign_Whole_Genome_Methylatio
Lab contact:
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Contact Policy:
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Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order:
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Complete and physician signed requisition required with pedigree and clear clinical diagnosis. Requisition available on lab website if required. Please draw 4-10ml EDTA whole blood and ship by overnight courier to the lab address (weekdays only)
Order URL
Order URL
Test service:
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Clinical Testing/Confirmation of Mutations Identified Previously
Comment: Requires prior phone contact to arrange for test development
Confirmation of research findings
Comment: Requires prior phone contact to arrange for test development
Custom Deletion/Duplication Testing
Comment: Available for any gene found on existing panels
Maternal cell contamination study (MCC)
Comment: Requires prior phone contact to arrange for consult
Comment: Requires prior phone contact to arrange for test development
Confirmation of research findings
Comment: Requires prior phone contact to arrange for test development
Custom Deletion/Duplication Testing
Comment: Available for any gene found on existing panels
Maternal cell contamination study (MCC)
Comment: Requires prior phone contact to arrange for consult
Test additional service:
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Custom mutation-specific/Carrier testing
Test development:
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Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)
Informed consent required:
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Decline to answer
Pre-test genetic counseling required:
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Decline to answer
Post-test genetic counseling required:
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Decline to answer
Recommended fields not provided:
Test strategy
Conditions
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Total conditions: 19
| Condition/Phenotype | Identifier |
|---|
Test Targets
Analytes
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Total analytes: 1
| Analyte | Associated Condition |
|---|
Methodology
Total methods: 1
Method Category
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Test method
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Instrument
Methylation analysis
Microarray
Illumina HiScan™SQ system
Clinical Information
Test purpose:
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Diagnosis;
Mutation Confirmation;
Risk Assessment;
Screening
Clinical utility:
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Establish or confirm diagnosis
View citations (1)
- Aref-Eshghi E, Bend EG, Colaiacovo S, Caudle M, Chakrabarti R, Napier M, Brick L, Brady L, Carere DA, Levy MA, Kerkhof J, Stuart A, Saleh M, Beaudet AL, Li C, Kozenko M, Karp N, Prasad C, Siu VM, Tarnopolsky MA, Ainsworth PJ, Lin H, Rodenhiser DI, Krantz ID, Deardorff MA, Schwartz CE, Sadikovic B. Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions. Am J Hum Genet. 2019;104(4):685-700. doi:10.1016/j.ajhg.2019.03.008. Epub 2019 Mar 28. PMID: 30929737.
Target population:
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Abnormalties detected using this initial screen may require additional targeted testing to confirm and further characterize the underlying genomic abnormality. 7q11.23 duplication AD Cerebeller Ataxia, Deafness, Narcolepsy (ADCADN) ADNP-related disorders/Hellsmoortal-Vander Aa syndrome Alpha-thalassemia/intellectual disability syndrome Angelman syndrome BAFopathy, including Coffin Siris & Nicolaides-Baraitser Beckwith-Wiedemann syndrome CHARGE syndrome Claes-Jenson syndrome Cornelia …
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Variant Interpretation:
What is the protocol for interpreting a variation as a VUS?
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Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely … View more
Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely … View more
Are family members with defined clinical status recruited to assess significance of VUS without charge?
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Decline to answer. Abnormalties detected using this initial screen may require additional targeted testing to confirm and further characterize the underlying genomic abnormality.
Decline to answer. Abnormalties detected using this initial screen may require additional targeted testing to confirm and further characterize the underlying genomic abnormality.
Will the lab re-contact the ordering physician if variant interpretation changes?
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No.
No.
Research:
Is research allowed on the sample after clinical testing is complete?
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Abnormalties detected using this initial screen may require additional targeted testing to confirm and further characterize the underlying genomic abnormality.
Abnormalties detected using this initial screen may require additional targeted testing to confirm and further characterize the underlying genomic abnormality.
Recommended fields not provided:
Clinical validity,
Sample negative report,
Sample positive report
Technical Information
Test Procedure:
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EpiSign is a methylation assay designed to readily identify proven and reproducible epigenetic signatures by assessing genome-wide methylation. EpiSign has multiple applications in the clinical setting. This test provides an additional diagnostic tool beyond the current sequencing and copy number technology paradigm. EpiSign can detect multiple known methylation abnormalities associated …
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View citations (1)
- Aref-Eshghi E, Bend EG, Colaiacovo S, Caudle M, Chakrabarti R, Napier M, Brick L, Brady L, Carere DA, Levy MA, Kerkhof J, Stuart A, Saleh M, Beaudet AL, Li C, Kozenko M, Karp N, Prasad C, Siu VM, Tarnopolsky MA, Ainsworth PJ, Lin H, Rodenhiser DI, Krantz ID, Deardorff MA, Schwartz CE, Sadikovic B. Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions. Am J Hum Genet. 2019;104(4):685-700. doi:10.1016/j.ajhg.2019.03.008. Epub 2019 Mar 28. PMID: 30929737.
Availability:
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Tests performed
Entire test performed in-house
Entire test performed in-house
Analytical Validity:
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. EpiSign Variant is a targeted review of the methylation data intended to resolve variants of uncertain clinical significance in genes with a known epigenetic signature (see list below). Pathogenic varients in these genes have an established unique signature. When present, this signature can be used to provide supporting evidence …
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View citations (1)
- Aref-Eshghi E, Bend EG, Colaiacovo S, Caudle M, Chakrabarti R, Napier M, Brick L, Brady L, Carere DA, Levy MA, Kerkhof J, Stuart A, Saleh M, Beaudet AL, Li C, Kozenko M, Karp N, Prasad C, Siu VM, Tarnopolsky MA, Ainsworth PJ, Lin H, Rodenhiser DI, Krantz ID, Deardorff MA, Schwartz CE, Sadikovic B. Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions. Am J Hum Genet. 2019;104(4):685-700. doi:10.1016/j.ajhg.2019.03.008. Epub 2019 Mar 28. PMID: 30929737.
Assay limitations:
Help
. EpiSign Variant is a targeted review of the methylation data intended to resolve variants of uncertain clinical significance in genes with a known epigenetic signature (see list below). Pathogenic varients in these genes have an established unique signature. When present, this signature can be used to provide supporting evidence …
View more
View citations (1)
- Aref-Eshghi E, Bend EG, Colaiacovo S, Caudle M, Chakrabarti R, Napier M, Brick L, Brady L, Carere DA, Levy MA, Kerkhof J, Stuart A, Saleh M, Beaudet AL, Li C, Kozenko M, Karp N, Prasad C, Siu VM, Tarnopolsky MA, Ainsworth PJ, Lin H, Rodenhiser DI, Krantz ID, Deardorff MA, Schwartz CE, Sadikovic B. Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions. Am J Hum Genet. 2019;104(4):685-700. doi:10.1016/j.ajhg.2019.03.008. Epub 2019 Mar 28. PMID: 30929737.
Proficiency testing (PT):
Is proficiency testing performed for this test?
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No
Description of PT method: Help
An extensive published validation process ensures proficiency at the outset. Mutation confirmation provides proficiency evidence in real time.
Description of internal test validation method: Help
By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case … View more
No
Description of PT method: Help
An extensive published validation process ensures proficiency at the outset. Mutation confirmation provides proficiency evidence in real time.
Description of internal test validation method: Help
By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case … View more
VUS:
Software used to interpret novel variations
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SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual with HGMD
Laboratory's policy on reporting novel variations Help
Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software. All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely … View more
SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual with HGMD
Laboratory's policy on reporting novel variations Help
Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software. All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely … View more
Recommended fields not provided:
Test Confirmation,
PT Provider,
Major CAP category, CAP category, CAP test list
Regulatory Approval
FDA Review:
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Category:
Not Applicable
Additional Information
Reviews:
Clinical resources:
Molecular resources:
Consumer resources:
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Patients and consumers
with specific questions about a genetic test should contact a health care provider or a genetics professional.