Cystic Fibrosis (CFTR) 165 Pathogenic Variants with Reflex to Sequencing

Background information for Cystic Fibrosis (CFTR), 165 Pathogenic Variants with Reflex to Sequencing:
Characteristics of Classic Cystic Fibrosis (CF): Chronic sino-pulmonary disease, gastrointestinal malabsorption/pancreatic insufficiency, and obstructive azoospermia. Symptoms of a CFTR-related disorder are often limited to a single organ system such as isolated pancreatitis, bilateral absence of the vas deferens, nasal polyposis, or bronchiectasis.
Incidence: 1 in 2,300 Ashkenazi Jewish, 1 in 2,500 Caucasians, 1 in 13,500 Hispanics, 1 in 15,100 African Americans, 1 in 35,100 Asians.
Inheritance: Autosomal recessive.
Penetrance: High for severe pathogenic variants, variable for moderate and mild pathogenic variants.
Cause of Classic CF: Two severe, or one severe and one moderate, pathogenic CFTR variants on opposite chromosomes.
Cause of CFTR-Related Disorders: Two pathogenic CFTR variants on opposite chromosomes in any of the following combinations; two mild, one mild and one severe or one mild and one moderate.
Pathogenic Variants Tested: Refer to Additional Technical Information document.
Clinical Sensitivity of CF 165-Variants Test: Ashkenazi Jewish 96 percent; Caucasian 92 percent; Hispanic 80 percent; African American 78 percent; Asian American 55 percent.
Clinical Sensitivity for Sequencing: 97 percent.
Methodology for 165-Variants Test: Polymerase Chain Reaction (PCR) and fluorescence monitoring.
Methodology for Sequencing: Bidirectional sequencing of the CFTR coding region and intron-exon boundaries.
Analytical Sensitivity & Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. CFTR promoter and regulatory region variants and large gene deletions/duplications and inversions will not be detected.