Test Catalog

Test Id : HPPAN

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Hereditary Pancreatitis Panel, Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirmation of suspected clinical diagnosis of familial or hereditary pancreatitis in patients with chronic pancreatitis

 

Identification of gene mutations contributing to pancreatitis in an individual or family

 

Identification of gene mutations to allow for predictive and diagnostic testing in family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes Sanger sequencing to evaluate for mutations in the PRSS1 gene, next-generation sequencing to evaluate for mutations in the CFTR, CTRC, and SPINK1 genes, and multiplex ligation-dependent probe amplification for the detection of large deletions and duplications within the CFTR gene.

Highlights

This test evaluates for mutations within the 4 most common genes associated with susceptibility to chronic pancreatitis: PRSS1, CFTR, CTRC, and SPINK1

 

This assay provides diagnostic confirmation of hereditary pancreatitis or identification of gene mutations contributing to pancreatitis in an individual or family

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing and Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Hereditary Pancreatitis Panel

Aliases
Lists additional common names for a test, as an aid in searching

Hereditary Pancreatitis

Pancreatitis

Familial Pancreatitis

CFTR

CTRC

SPNK1

PRSS1

Next Gen Sequencing Test

Specimen Type
Describes the specimen type validated for testing

Varies

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

3. If not ordering electronically, complete, print, and send a Gastroenterology and Hepatology Client Test Request (T728) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
Frozen
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirmation of suspected clinical diagnosis of familial or hereditary pancreatitis in patients with chronic pancreatitis

 

Identification of gene mutations contributing to pancreatitis in an individual or family

 

Identification of gene mutations to allow for predictive and diagnostic testing in family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes Sanger sequencing to evaluate for mutations in the PRSS1 gene, next-generation sequencing to evaluate for mutations in the CFTR, CTRC, and SPINK1 genes, and multiplex ligation-dependent probe amplification for the detection of large deletions and duplications within the CFTR gene.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hereditary pancreatitis (HP) is defined as 2 or more individuals in a family affected with pancreatitis involving at least 2 generations. Mutations in several genes, including PRSS1, CFTR, CTRC, and SPINK1 have demonstrated genetic susceptibility to chronic pancreatitis. Disease susceptibility may be monogenic, as is the case with PRSS1, digenic or multigenic, and multifactorial in which multiple genes and environmental factors play a role in disease expression.

 

PRSS1:

The most common monogenic cause of HP is the presence of a mutation in the cationic trypsinogen (PRSS1) gene. Mutations in the PRSS1 gene are inherited in an autosomal dominant manner. It has been reported that as many as 80% of patients with symptomatic hereditary pancreatitis have a causative PRSS1 mutation. HP cannot be clinically distinguished from other forms of pancreatitis. However, PRSS1 mutations are generally restricted to individuals with a family history of pancreatitis and are infrequently found in patients with alcohol-induced or tropical pancreatitis. Although several mutations have been identified, the R122H, N29I, and A16V mutations are the most common disease-causing mutations in PRSS1 associated with HP. Data suggests that the R122H mutation results in more severe disease and earlier onset of symptoms than the A16V mutation. Patients with HP are also at an increased risk for developing pancreatic cancer. Studies have estimated the lifetime risk of developing pancreatic cancer to be as high as 40%.

 

SPINK1:

Biallelic mutations in the SPINK1 gene have been associated with increased susceptibility to chronic pancreatitis especially in families without PRSS1 mutations; however, it is unknown if biallelic mutations alone are sufficient to cause chronic pancreatitis. Additionally, heterozygous SPINK1 mutations appear to modify disease severity when observed in combination with mutations in other genes. Unlike PRSS1 mutations, SPINK1 mutations have been associated with alcohol-induced and tropical pancreatitis.

 

CFTR:

Pancreatitis is a known manifestation of an atypical CFTR-related disorder in which 2 mutations in the CFTR gene are identified. However, CFTR mutations can also co-occur with mutations in CTRC, SPINK1, or CASR to confer pancreatitis disease susceptibility. When observed in the context of a SPINK1 mutation, for example, heterozygous mutations in CFTR are associated with a 2- to 5-fold increased risk for pancreatitis as compared to the general population.

 

CTRC:

Mutations in CTRC have been observed in individuals with chronic pancreatitis in association with other risk factors such as mutations in CFTR or SPINK1 or specific environmental risk factors. Thus, chronic pancreatitis may be attributable to the presence of CTRC mutations in the context of other risk factors as opposed to CTRC mutations alone.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations will be evaluated according to the American College of Medical Genetics and Genomics (AMCG) recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Some individuals with a diagnosis of hereditary pancreatitis and/or involvement of the genes tested may have a mutation that is not identified by this method (eg, large genomic deletions or duplications, promoter mutations, deep intronic mutations). The absence of a mutation, therefore, does not eliminate the possibility of a diagnosis of hereditary pancreatitis or susceptibility to pancreatitis. For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene mutation in an affected family member.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

 

Technical limitations:

In some cases, DNA variants of undetermined significance may be identified.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

In addition to disease-related probes, the multiplex ligation-dependent probe amplification (MLPA) technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

 

Evaluation tools:

Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently unvalidated.

 

Unless reported or predicted to cause disease, alterations in protein coding genes that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.

 

Reclassification of Variants-Policy:

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. At this time, it is not standard practice for the laboratory to systematically review likely pathogenic alterations or variants of uncertain significance that have been previously detected and reported. 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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: 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 May;17(5):405-424

2. Raphael KL, Willingham FF: Hereditary pancreatitis: current perspectives. Clin Exp Gastroenterol. 2016 Jul 26;9:197-207

3. Solomon S, Whitcomb DC: Genetics of pancreatitis: an update for clinicians and genetic counselors. Curr Gastroenterol Rep 2012;14(2):112-117

4. Ellis I: Genetic counseling for hereditary pancreatitis-the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1. Gastroenterol Clin North Am 2004;33:839-854

5. Pancreatitis Overview. In GeneReviews-NCBI Bookshelf. 2014 Mar 13. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington,. Seattle WA. 1993-2018. Accessed January 2019. Available at URL: http://www.ncbi.nlm.nih.gov/books/NBK190101/

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing and/or Sanger sequencing is used to test for the presence of a mutation in all coding regions and intron/exon boundaries of the PRSS1, CFTR, CTRC, and SPINK1 genes. Sequencing of genomic regions encompassing select clinically relevant intronic mutations within the CFTR gene is also performed. Additionally, gene dosage analysis by multiplex ligation-dependent probe amplification (MLPA) is used to test for the presence of large deletions and duplications in the CFTR gene. Sanger sequencing is used to confirm alterations detected by next-generation sequencing when appropriate.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Performed weekly

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

14 to 20 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available) Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81222

81223

81404 x2

81405

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HPPAN Hereditary Pancreatitis Panel In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
52581 Result Summary 50397-9
52582 Result 82939-0
52583 Interpretation 69047-9
52584 Additional Information 48767-8
52585 Specimen 31208-2
52586 Source 31208-2
52587 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports