Massively Parallel Sequencing/Sequencing
- Use for individuals with a personal history of idiopathic pancreatitis
- Use to detect sequence variants in the CFTR, CTRC, PRSS1, and SPINK1 genes
Massively Parallel Sequencing
- Testing for a known familial sequence variant by sequencing gene of interest. A copy of the family member’s test result documenting the familial gene variant is REQUIRED.
- Not all common CFTR variants are covered by this test; please see the Targeted Sequencing Gene List for detailed information regarding the limitations of sequencing.
- To determine if the variant(s) of interest are detectable by this assay, contact an ARUP genetic counselor at 800-242-2787.
Pancreatitis is a relatively common disorder with multiple etiologies that causes inflammation in the pancreas. Acute pancreatitis (AP) is a result of sudden inflammation, and patients may present with increased pancreatic enzyme concentrations. Chronic pancreatitis (CP) is a syndrome of progressive inflammation that may lead to permanent damage to pancreatic structure and function. Genetic testing can be utilized to determine a genetic cause of idiopathic or hereditary AP or CP and/or to assess risk of disease in family members.
Symptoms and Etiology
- CFTR (NM_000492), CTRC (NM_007272), PRSS1 (NM_002769), SPINK1 (NM_003122)
- PRSS1: autosomal dominant with gain-of-function variants
- CFTR, CTRC, SPINK1: autosomal recessive/digenic
This test is performed using the following sequence of steps:
- Selected genomic regions, primarily coding exons and exon-intron boundaries, from the targeted genes are isolated from extracted genomic DNA using a probe-based hybrid capture enrichment workflow.
- Enriched DNA is sequenced by massively parallel sequencing (MPS; also known as next generation sequencing [NGS]) followed by paired-end read alignment and variant calling using a custom bioinformatics pipeline.
- Sanger sequencing is performed as necessary to fill in regions of low coverage or known low quality, and in certain other situations to confirm variant calls.
CFTR, CTRC, PRSS1, and SPINK1 pathogenic variants which contribute to or explain idiopathic pancreatitis: ~48%
|Variant Class||Analytical Sensitivity (PPA) Estimatea (%)
and 95% Credibility Region (%)
|Analytical Specificity (NPA) (%)|
Deletions 1-10 bpb
Insertions 1-10 bpb
aGenes included on this test are a subset of a larger methods-based validation from which the PPA values are derived.
bVariants greater than 10 bp may be detected, but the analytical sensitivity may be reduced.
bp, base pairs; NPA, negative percent agreement; PPA, positive percent agreement; SNVs, single nucleotide variants
One of the following:
|Negative||No pathogenic variants detected in any of the genes; reduces the risk for hereditary pancreatitis but genetic etiology is not excluded|
|Uncertain||Variant(s) of uncertain clinical significance detected; may be disease-causing or benign|
- A negative result does not exclude a genetic etiology for pancreatitis.
- Diagnostic errors can occur due to rare sequence variations.
- Interpretation of this test result may be impacted if this patient has had an allogeneic stem cell transplantation.
- The following will not be evaluated:
- Variants outside the coding regions and intron-exon boundaries of targeted genes
- Regulatory region and deep intronic variants other than 5T (IVS8), c.1680-886A>G (c.1679+1.6kbA>G), and c.3718-2477C>T in the CFTR gene
- Large deletions/duplications in any of the tested genes
- Variants in currently unknown genes that may be associated with pancreatitis
- The following may not be detected:
- Deletions/duplications/insertions of any size by massively parallel sequencing
- Noncoding transcripts
- Low-level somatic variants
- Certain other variants due to technical limitations in the presence of pseudogenes or repetitive/homologous regions
Conwell DL, Lee LS, Yadav D, et al. American Pancreatic Association practice guidelines in chronic pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014;43(8):1143-1162.
GeneReviews - pancreatitis overview
Shelton C, LaRusch J, Whitcomb DC. Pancreatitis overview. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington, Seattle; 1993-2022. [Updated: Jul 2020; Accessed: Feb 2022]
GeneReviews - PRSS1-related hereditary pancreatitis
Shelton C, Solomon S, LaRusch J, et al. PRSS1-related hereditary pancreatitis. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews, University of Washington, Seattle; 1993-2020. [Last Update: Apr 2019; Accessed: Feb 2022]
Rebours V, Boutron-Ruault MC, Schnee M, et al. The natural history of hereditary pancreatitis: a national series. Gut. 2009;58(1):97-103.
Masson E, Chen JM, Audrézet MP, et al. A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. PLoS One. 2013;8(8):e73522.
Gupte A, Goede D, Tuite R, et al. Chronic pancreatitis. BMJ. 2018;361:k2126.
LaRusch J, Whitcomb DC. Genetics of pancreatitis. Curr Opin Gastroenterol. 2011;27(5):467-474.
Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144(6):1252-1261.