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  • Test code: 06220
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Cystic Fibrosis Newborn Screening Confirmation Test

Test description

The Invitae Cystic Fibrosis Newborn Screening Confirmation test analyzes the CFTR gene; which is associated with cystic fibrosis (CF).

Pathogenic variants in the CFTR gene inhibit the function of chloride channels across cell membranes. This disrupts the ability of the cells to regulate the flow of water and chloride ions and results in the buildup of a thick sticky mucus that can clog airways and organs such as the pancreas and intestine.

Genetic testing for CF is particularly useful because of the strong genotypic/phenotypic correlations in this gene. The combination of specific variants may correlate to specific expected outcomes for the patient.

Analysis includes the polymorphic TG/T tract within intron 9 as well as known promoter, 5’ UTR, 3’UTR, and intronic HGMD variants (including, but not limited to, c.3718-2477C>T, also known as 3849+10kbC>T and c.3717+12191C>T in the literature). Variants in these regions will be interpreted and only included in the primary report if classified as likely pathogenic, pathogenic, or in some cases, variant of uncertain significance. Polymorphisms classified as benign or likely benign are available upon request.

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Primary panel (1 gene)
  • cystic fibrosis (CF)
    • cystic fibrosis-related diabetes mellitus (CFRDM) — individuals with CF who experience insulin deficiency and who may or may not be insulin deficient
    • congenital absence of the vas deferens (CAVD) – abnormal development of the vas deferens, leading to male infertility; approximately 80% of men with CAVD have at least one identifiable mutation in CFTR

Cystic fibrosis (CF) is a complex multisystemic disorder caused by the buildup of thick, viscous secretions on the lining (epithelia) of many different organ systems. This buildup damages organ function over time. Classically affected individuals often present with pulmonary symptoms, including lower airway inflammation, recurrent pulmonary infections, airway damage, and the buildup of scar tissue in the lungs (lung fibrosis). Historically, pulmonary failure was a common cause of childhood morbidity, but with improved preventive treatment, individuals with CF now frequently live into adulthood.

Individuals with CF may also present with digestive problems associated with the pancreas and the intestine. The reduced production of insulin and digestive enzymes by the pancreas (pancreatic insufficiency) can lead to nutritional deficiencies. In infants with CF, excess mucus production in the intestine can cause a blockage called meconium ileus.

CAVD is a disorder that occurs in males; the tubes that carry sperm out of the testes (vas deferens) develop abnormally. Without the assistance of reproductive technology, this disorder results in male infertility. CAVD is sometimes observed in males with CF, though it can also occur independently.

CFTR-related disorders encompasses a broad clinical spectrum from single organ manifestations to individuals with abnormal IRT and/or sweat test results, but mild or absent clinical symptoms.

CFTR is the only gene known to be associated with cystic fibrosis and the CFTR-related disorders. Sequencing identifies more than 98% of CFTR pathogenic variants.

All CFTR-related conditions are inherited in an autosomal recessive pattern.

CF is considered to have incomplete penetrance and variable expression. Genotype/phenotype correlations have been well studied and account for much of this variability.

In the United States, cystic fibrosis occurs most frequently in the Caucasian population, with an incidence of 1 in 2,500 to 1 in 3,500 newborns. CF is less common in other ethnic groups, occurring in approximately 1 in 15,000 to 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.

This test is intended for any individual with an elevated immunoreactive trypsinogen (IRT) on newborn screening (NBS), a positive sweat chloride test (sweat test), or a suspected diagnosis of a cystic fibrosis based on clinical presentation.

Assay and technical information

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.

Assay notes

*Analysis includes the polymorphic TG/T tract within intron 9 as well as known promoter, 5’ UTR, 3’UTR, and intronic HGMD variants (including, but not limited to, c.3718-2477C>T, also known as 3849+10kbC>T and c.3717+12191C>T in the literature). Variants in these regions will be interpreted and only included in the primary report if classified as likely pathogenic, pathogenic, or in some cases, variant of uncertain significance. Polymorphisms classified as benign or likely benign are available upon request.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CFTR* NM_000492.3

CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TG[12]T[5] (also known as T5TG12), c.1210-34TG[11]T[5] (also known as T5TG11), and c.1679+1634A>G.