RET Full Gene Analysis - Clinical Genetic Test - GTR

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RET Full Gene Analysis

Clinical Genetic Test

offered by

Mayo Clinic Laboratories

View lab's test page

GTR Test Accession: GTR000597357.2

INHERITED DISEASEDYSMORPHOLOGYNERVOUS SYSTEM ... View more

Last updated in GTR: 2024-04-15

Last annual review date for the lab: 2023-05-30

At a Glance

Test purpose:

Diagnosis; Predictive

Conditions (2):

Multiple endocrine neoplasia, type 2; Aganglionic megacolon

Genes (1):

RET (10q11.21)

Methods (1):

Molecular Genetics - Sequence analysis of the entire coding region: Next-Generation (NGS)/Massively parallel sequencing (MPS)

Target population:

Evaluation for patients with a personal or family history suggestive …

Clinical validity:

Not provided

Clinical utility:

Establish or confirm diagnosis; Guidance for management; Predictive risk information for patient and/or family members

Ordering Information

Offered by:

Mayo Clinic Laboratories
View lab's website
View lab's test page

Test short name:

RETZZ

Specimen Source:

Peripheral (whole) blood
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Dentist
Licensed Physician
Nurse Practitioner
Physician Assistant
Public Health Mandate
Registered Nurse

Test Order Code:

RETZZ
View other test codes

LOINC codes:

**LOINC codes notice

CPT codes:

81406

**AMA CPT codes notice

Lab contact:

Megan Hoenig, MS, MPH, Certified Genetic counselor, CGC, Genetic Counselor
GCMolgen@mayo.edu
1-800-533-1710

Contact Policy:

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:

https://www.mayocliniclabs.com/test-catalog/Specimen/614587
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
OrderCode: FMTT

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Based on applicable state law

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Test strategy

Conditions

Total conditions: 2

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 1

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 1

Method Category

Test method

Instrument

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Illumina NovaSeq 6000

Clinical Information

Test purpose:

Diagnosis; Predictive

Clinical utility:

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:

Evaluation for patients with a personal or family history suggestive of a multiple endocrine neoplasia type 2 (MEN2) or Hirschsprung disease (HSCR). Establishing a diagnosis of MEN2 or HSCR allowing for targeted cancer surveillance based on associated risks. Identifying variants within genes known to be associated with MEN2 or HSCR … View more

View citations (7)

de Pontual L, Pelet A, Trochet D, Jaubert F, Espinosa-Parrilla Y, Munnich A, Brunet JF, Goridis C, Feingold J, Lyonnet S, Amiel J. Mutations of the RET gene in isolated and syndromic Hirschsprung's disease in human disclose major and modifier alleles at a single locus. J Med Genet. 2006;43(5):419-23. doi:10.1136/jmg.2005.040113. Epub 2006 Jan 27. PMID: 16443855.
A complex additive model of inheritance for Hirschsprung disease is supported by both RET mutations and predisposing RET haplotypes. Ruiz-Ferrer M, et al. Genet Med. 2006;8(11):704-10. doi:10.1097/01.gim.0000245632.06064.f1. PMID: 17108762.
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.
Multiple endocrine neoplasia type 2: an overview. Moline J, et al. Genet Med. 2011;13(9):755-64. doi:10.1097/GIM.0b013e318216cc6d. PMID: 21552134.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. doi:10.1038/gim.2015.30. Epub 2015 Mar 05. PMID: 25741868.
Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Wells SA, et al. Thyroid. 2015;25(6):567-610. doi:10.1089/thy.2014.0335. PMID: 25810047.
NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018. Haddad RI, et al. J Natl Compr Canc Netw. 2018;16(12):1429-1440. doi:10.6004/jnccn.2018.0089. PMID: 30545990.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
All detected variants are evaluated according to the most recent American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Are family members with defined clinical status recruited to assess significance of VUS without charge?
Yes. Contact lab for details

Will the lab re-contact the ordering physician if variant interpretation changes?
No. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Research:

Is research allowed on the sample after clinical testing is complete?
Research testing is only performed under IRB approved protocol with an opt-out policy in place.

Recommended fields not provided:

Clinical validity, Sample negative report, Sample positive report

Technical Information

Test Procedure:

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the RET gene analyzed, as well as some other regions that have known pathogenic variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At … View more

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

At least 99% of the bases are covered at a read depth >30X. Sensitivity is estimated at >99% for single nucleotide variants, >94% for indels up to 39 base pairs, >95% for deletions up to 75 base pairs and insertions up to 47 base pairs.

Assay limitations:

Clinical Correlations: Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test … Clinical Correlations: Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals. To discuss the availability of further testing options or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 800-533-1710. Technical Limitations: Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered. There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria. This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Insertions/deletions (indels) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller indels. Deletion/Duplication Analysis: This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected. This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor at 800-533-1710. If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant. Reclassification of Variants: At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Variant Evaluation: Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline. Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported. Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement. View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Alternative Assessment

Description of PT method:
Platform covered

Description of internal test validation method: Help
This test was laboratory developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements

VUS:

Software used to interpret novel variations
Variants may be analyzed using any combination of the following: Alamut, REVEL, Polyphen-2, SIFT, AGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, SpliceAI, gene-specific online databases, ISCA, UCSC Genome Browser

Laboratory's policy on reporting novel variations
All novel alterations and copy number variants are evaluated for potential pathogenicity and included in the written report, accordingly.

Recommended fields not provided:

Test Confirmation, Citations to support assay limitations, Citations to support internal test validation method, Citations for Analytical validity, PT Provider, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Reviews in PubMed