Multiple Endoctine Neoplasia Type 2 (RET)
GTR Test Accession: Help GTR000021494.6
CAP
INHERITED DISEASEINHERITED DISEASE SUSCEPTIBILITYCANCER ... View more
Last updated in GTR: 2024-02-07
Last annual review date for the lab: 2024-02-07 LinkOut
At a Glance
Diagnosis; Mutation Confirmation; Pre-symptomatic; ...
Multiple endocrine neoplasia, type 2; Familial medullary thyroid carcinoma; Hirschsprung disease, susceptibility to, 1; ...
Genes (1): Help
RET (10q11.21)
Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
RET is the only gene in which mutations are known …
Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome …
Establish or confirm diagnosis; Guidance for management; Predictive risk information for patient and/or family members
Ordering Information
Offered by: Help
Molecular Genetics Laboratory
View lab's website
View lab's test page
Test short name: Help
MEN2
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Licensed Physician
Test Order Code: Help
Multiple Endocrine Neoplasia Type 2(RET)
Lab contact: Help
Gavin Giles, MSc, Administrator
gavin.giles@lhsc.on.ca
+1-519-685-8500 x36339
Contact Policy: Help
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: Help
Please complete the requisition found on the website and ensure it is signed by the referring physician
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Custom Sequence Analysis
Test additional service: Help
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
Decline to answer
Test strategy: Help
All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; … View more
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Conditions Help
Total conditions: 5
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 1
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 2
Method Category Help
Test method Help
Instrument
Deletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Illumina MiSeq/NextSeq
Sequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Applied Biosystems 3730 capillary sequencing instrument
Illumina MiSeq/NextSeq
Clinical Information
Test purpose: Help
Diagnosis; Mutation Confirmation; Pre-symptomatic; Predictive; Prognostic
Clinical validity: Help
Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome of multiple endocrine neoplasms, including medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas. MEN2B (162300), characterized by MTC with or without pheochromocytoma and with characteristic clinical abnormalities such as ganglioneuromas of the lips, tongue and colon, but without hyperparathyroidism, is … View more
Clinical utility: Help
Establish or confirm diagnosis
View citations (2)
  • Eng C, Plitt G. Multiple Endocrine Neoplasia Type 2. 1999 Sep 27 [updated 2023 Aug 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301434.
  • https://www.ncbi.nlm.nih.gov/books/NBK1257

Guidance for management
View citations (2)
  • Eng C, Plitt G. Multiple Endocrine Neoplasia Type 2. 1999 Sep 27 [updated 2023 Aug 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301434.
  • https://www.ncbi.nlm.nih.gov/books/NBK1257

Predictive risk information for patient and/or family members
View citations (2)
  • Eng C, Plitt G. Multiple Endocrine Neoplasia Type 2. 1999 Sep 27 [updated 2023 Aug 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301434.
  • https://www.ncbi.nlm.nih.gov/books/NBK1257

Target population: Help
RET is the only gene in which mutations are known to cause MEN type 2. Molecular genetic testing of RET identifies disease-causing mutations in 98% of individuals with MEN 2A, more than 98% of individuals with MEN 2B, and in about 95% of families with FMTC.
View citations (1)
  • Eng C, Plitt G. Multiple Endocrine Neoplasia Type 2. 1999 Sep 27 [updated 2023 Aug 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301434.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >1000x mean read depth coverage, with a minimum 200x coverage at a single nucleotide resolution. This assay meets the sensitivity and … View more

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Not provided.
Recommended fields not provided:
Technical Information
Test Procedure: Help
All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; … View more
View citations (1)
  • Schenkel LC, Kerkhof J, Stuart A, Reilly J, Eng B, Woodside C, Levstik A, Howlett CJ, Rupar AC, Knoll JHM, Ainsworth P, Waye JS, Sadikovic B. Clinical Next-Generation Sequencing Pipeline Outperforms a Combined Approach Using Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification in Targeted Gene Panel Analysis. J Mol Diagn. 2016;18(5):657-667. doi:10.1016/j.jmoldx.2016.04.002. Epub 2016 Jul 02. PMID: 27376475.
Test Confirmation: Help
Mutations identified are repeated in an independent assay using either Sanger sequence or MLPA
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis, >99%
View citations (1)
  • Schenkel LC, Kerkhof J, Stuart A, Reilly J, Eng B, Woodside C, Levstik A, Howlett CJ, Rupar AC, Knoll JHM, Ainsworth P, Waye JS, Sadikovic B. Clinical Next-Generation Sequencing Pipeline Outperforms a Combined Approach Using Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification in Targeted Gene Panel Analysis. J Mol Diagn. 2016;18(5):657-667. doi:10.1016/j.jmoldx.2016.04.002. Epub 2016 Jul 02. PMID: 27376475.
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP
VUS:
Software used to interpret novel variations Help
(SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual).

Laboratory's policy on reporting novel variations Help
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 benign, benign) are not reported, but are available upon request.
Recommended fields not provided:
Regulatory Approval
FDA Review: Help
Category: Not Applicable
Additional Information

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