The Invitae Chronic Pancreatitis Panel analyzes five genes associated with an increased risk of chronic pancreatitis (CP), a condition that results in irreversible morphological changes and impairment of both exocrine and endocrine functions. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive test for chronic pancreatitis.
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant may also guide testing and diagnosis of at-risk relatives.
CASR CFTR CTRC PRSS1 SPINK1
CASR CFTR CTRC PRSS1 SPINK1
The pancreas is responsible for synthesizing enzymes for protein, fat, and carbohydrate digestion in the intestines and for producing insulin and glucagon for maintaining blood-sugar balance. Chronic pancreatitis is a progressive inflammatory disorder in which overly active digestive enzymes destroy the pancreatic secretory cells. The primary features of chronic pancreatitis include intractable pain and maldigestion, followed by diabetes mellitus and malnutrition with advancing disease.
Alcoholism is the leading cause of chronic pancreatitis and accounts for approximately 50% of all cases worldwide. Approximately 10% of cases with alcoholic chronic pancreatitis (ACP) have been found to have a pathogenic variant in one of the genes on this panel, and pathogenic variants in these genes have been identified in approximately 90% of individuals with idiopathic (previously unexplained) chronic pancreatitis (ICP).
The inheritance pattern of chronic pancreatitis varies by gene:
CFTR is also known to cause autosomal recessive cystic fibrosis (CF) and congenital bilateral absence of vas deferens (CBAVD).
The prevalence of chronic pancreatitis is ~1 in 4,000 on average, with considerably higher rates (~1 in 1,000) in southern India.
Testing for chronic pancreatitis may be considered in any individual with a personal and/or family history of:
Consensus recommendations on medical management have been proposed:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TGT (also known as T5TG12), c.1210-34TGT (also known as T5TG11), and c.1679+1634A>G.