Confirmation of a clinical diagnosis of cystic fibrosis
Risk refinement via carrier screening for individuals in the general population
Prenatal diagnosis or familial variant testing when the familial variants are included in the 106-variant panel listed in Clinical Information
Risk refinement via carrier screening for individuals with a family history when familial mutations are not available
Identification of patients who may respond to CFTR potentiator therapy
This 106-variant panel includes the 23 variants recommended by the American College of Medical Genetics and Genomics (ACMG).
For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.
See Cystic Fibrosis Molecular Diagnostic Testing Algorithm in Special Instructions.
Multiplex Polymerase Chain Reaction (PCR)/Mass Array
CF
CFPB
CFTR (Cystic Fibrosis Transmembrane Conductance)
Congenital Bilateral Absence of the Vas deferens
Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis, Prenatal Diagnosis
Pancreatitis
For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.
See Cystic Fibrosis Molecular Diagnostic Testing Algorithm in Special Instructions.
Varies
If familial variants are not included in this 106-variant panel, order FMTT / Familial Mutation, Targeted Testing, Varies
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen preferred to arrive within 96 hours of collection.
Additional Information: Patient education brochures in English (T548) and Spanish (T563) are available upon request.
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.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 2.5 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Prenatal Specimens
Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. Central time on Friday in order to be processed appropriately.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional information:
1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks is required to culture amniotic fluid before genetic testing can occur.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Refrigerated
Additional information:
1. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Genetic Test. An additional 2 to 3 weeks is required to culture chorionic villi before genetic testing can occur.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Confluent cultured cells
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information: All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Blood spot
Supplies: Card - Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper or Blood Spot Collection Card
Specimen Volume: 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient 1 year of age and older is a fingerstick. See Dried Blood Spot Collection Tutorial for how to collect blood spots via fingerstick.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. For collection instructions, see Blood Spot Collection Instructions.
2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).
3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).
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
Amniotic fluid: 10 mL
Blood: 0.5 mL
Chorionic Villi: 5 mg
Blood Spots: 5 punches, 3-mm diameter
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies (preferred) |
Confirmation of a clinical diagnosis of cystic fibrosis
Risk refinement via carrier screening for individuals in the general population
Prenatal diagnosis or familial variant testing when the familial variants are included in the 106-variant panel listed in Clinical Information
Risk refinement via carrier screening for individuals with a family history when familial mutations are not available
Identification of patients who may respond to CFTR potentiator therapy
This 106-variant panel includes the 23 variants recommended by the American College of Medical Genetics and Genomics (ACMG).
For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.
See Cystic Fibrosis Molecular Diagnostic Testing Algorithm in Special Instructions.
Cystic fibrosis (CF), in the classic form, is a severe autosomal recessive disorder characterized by a varied degree of chronic obstructive lung disease and pancreatic enzyme insufficiency. The incidence of CF varies markedly among different populations, as does the variant detection rate for the variant screening assay. To date, over 1500 variants have been described within the CF gene, named cystic fibrosis transmembrane conductance regulator (CFTR). The most common variant, deltaF508, accounts for approximately 67% of the variants worldwide and approximately 70% to 75% in a North American White population. Most of the remaining variants are rather rare, although some show a relatively higher prevalence in certain ethnic groups or in some atypical presentations of CF such as congenital bilateral absence of the vas deferens (CBAVD). Variants detected by this assay include the 23 variants recommended by the American College of Medical Genetics and Genomics as well as 83 other variants.
Of note, CFTR potentiator therapies may improve clinical outcomes for patients with a clinical diagnosis of CF and at least one copy of the G178R, G551S, G551D, S549N, S549R, G1244E, S1251N, S1255P, or G1349D variant. The G178R, S549N, S549R, S551D, and S1251N variants are included in this test.
These 106 variants account for approximately 91% of CF chromosomes in a Northern European White population. Detection rates for several ethnic and racial groups are listed in the table below. Note that interpretation of test results and risk calculations are also dependent on clinical information and family history.
Racial or ethnic group | Carrier frequency | Variant detection rate* |
African American | 1/65 | 81% |
Ashkenazi Jewish | 1/25 | 97% |
Asian American (excluding individuals of Japanese ancestry) | 1/90 | 54% |
Mixed European | 1/25 | 82% |
Eastern European | 1/25 | 77% |
French Canadian | 1/25 | 91% |
Hispanic American | 1/46 | 82% |
Northern European | 1/25 | 91% |
Southern European | 1/25 | 79% |
*Rates are for classical CF. Rates are lower for atypical forms of CF and for CBAVD.
CFTR variants listed below are included in this panel.
Deletion exons 2-3 | Exon 11: R553X |
Intron 2: 296+2 T>A | Exon 11: A559T |
Exon 3: E60X | Exon 11: R560T |
Exon 3: R75X | Intron 11: 1811+1.6kb A>G |
Exon 3: G85E | Intron 11: 1812-1 G>A |
Exon 3: 394_395delTT | Intron 12: 1898+1 G>A |
Intron 3: 405+1 G>A | Intron 12: 1898+1 G>T |
Intron 3: 406-1 G>A | Intron 12: 1898+1 G>C |
Exon 4: E92X | Intron 12: 1898+5 G>T |
Exon 4: 444delA | Exon 12: P574H |
Exon 4: 457TAT>G | Exon 13: 1949del84 |
Exon 4: R117H | Exon 13: 2043delG |
Exon 4: R117C | Exon 13: 2055del9>A |
Exon 4: Y122X | Exon 13: 2105del13ins5 |
Exon 4: 574delA | Exon 13: 2108delA |
Intron 4: 621+1 G>T | Exon 13: 2143delT |
Exon 5: 663delT | Exon 13: 2183_2184delAAinsG |
Exon 5: G178R | Exon 13: 2184delA |
Intron 5: 711+1 G>T | Exon 13: 2184insA |
Intron 5: 711+5 G>A | Exon 13: R709X |
Intron 5: 712-1 G>T | Exon 13: K710X |
Exon 6a: H199Y | Exon 13: 2307insA |
Exon 6a: P205S | Exon 13: R764X |
Exon 6a: L206W | Intron 14b: 2789+5 G>A |
Exon 6a: 852del22 | Exon 15: 2869insG |
Exon 6b: 935delA | Exon 15: Q890X |
Exon 6b: 936delTA | Intron 16: 3120+1 G>A |
Exon 7: deltaF311 | Exon 17a: 3171delC |
Exon 7: 1078delT | Exon 17a: 3199del6 |
Exon 7: G330X | Exon 17b: R1066C |
Exon 7: R334W | Exon 17b: W1089X (TGG>TAG) |
Exon 7: T338I | Exon 17b: Y1092X (C>G) |
Exon 7: R347P | Exon 17b: Y1092X (C>A) |
Exon 7: R347H | Exon 17b: M1101K |
Exon 7: R352Q | Exon 17b: M1101R |
Exon 7: Q359K | Exon 18: D1152H |
Exon 7: T360K | Exon 19: R1158X |
Exon 8: 1288insTA | Exon 19: R1162X |
Exon 9: A455E | Exon 19: 3659delC |
Exon 10: S466X (C>A) | Exon 19: 3667del4 |
Exon 10: S466X (C>G) | Exon 19: S1196X |
Exon 10: G480C | Exon 19: W1204X (TGG>TAG) |
Exon 10: Q493X | Exon 19: 3791delC |
Exon 10: deltaI507 | Exon 19: Q1238X |
Exon 10: deltaF508 | Intron 19: 3849+10kb C>T |
Exon 10: 1677delTA | Exon 20: 3876delA |
Exon 10: C524X | Exon 20: S1251N |
Intron 10: 1717-1 G>A | Exon 20: S1255X |
Exon 11: G542X | Exon 20: 3905insT |
Exon 11: S549N | Exon 20: W1282X (TGG>TGA) |
Exon 11: S549R (T>G) | Exon 21: 4016insT |
Exon 11: G551D | Exon 21: N1303K (C>A) |
Exon 11:Q552X | Exon 21: N1303K (C>G) |
See Cystic Fibrosis Molecular Diagnostic Testing Algorithm in Special Instructions for additional information.
An interpretive report will be provided.
An interpretive report will be provided.
This assay will not detect all of the variants that cause cystic fibrosis. Therefore, the absence of a detectable variant does not rule out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.
Rare alterations (ie, 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 rare cases, DNA alterations of undetermined significance may be identified.
1. Quint A, Lerer I, Sagi M, Abeliovich D: Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to carrier screening. Am J Med Genet A. 2005;136(3):246-248. doi: 10.1002/ajmg.a.30823
2. Bobadilla JL, Macek M, Fine FP, Farrell PM: Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum Mutat. 2002;19(6):575-606. doi: 10.1002/humu.10041
3. Sugarman EA, Rohlfs EM, Silverman LM, Alitto BA: CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. Genet Med. 2004;6(5):392-399. doi: 10.1097/01.gim.0000139503.22088.66
4. Watson MS, Cutting GR, Desnick RJ, et al: Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med. 2004;6(5):387-391. doi: 10.1097/01.gim.0000139506.11694.7c
5. Heim RA, Sugarman EA, Allitto BA: Improved detection of cystic fibrosis mutations in the heterozygous U.S. population using an expanded, pan-ethnic mutation panel. Genet Med. 2001;3(3):168-176. doi: 10.1097/00125817-200105000-00004
6. De Boeck K, Munck A, Walker S, et al: Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros. 2014 Dec;13(6):674-680. doi: 10.1016/j.jcf.2014.09.005
The multiplex polymerase chain reaction (PCR)-based assay utilizing the Agena Mass Array platform is used to detect 106 variants, including the 23 variants specified in the American College of Medical Genetics and Genomics (ACMG) standards for population-based carrier screening. The variants are as follows: deltaF508, deltaI507, G542X, G85E, R117H, W1282X (TGG>TGA), 621+1 G>T, 711+1 G>T, N1303K (C>A), N1303K (C>G), R334W, R347P, A455E, 1717-1 G>A, R553X, R560T, G551D, 1898+1 G>A, 2184delA, 2789+5 G>A, 3120+1 G>A, R1162X, 3659delC, and 3849+10kb C>T, the deletion of exons 2-3, 296+2 T>A, E60X, R75X, 394_395delTT, 405+1 G>A, 406-1 G>A, E92X, 444delA, 457TAT>G, R117C, Y122X, 574delA, 663delT, G178R, 711+5 G>A, 712-1 G>T, H199Y, P205S, L206W, 852del22, 935delA, 936delTA, deltaF311, 1078delT, G330X, T338I, R347H, R352Q, Q359K, T360K, 1288insTA, S466X (C>A), S466X (C>G), G480C, Q493X, 1677delTA, C524X, S549N, S549R (T>G), Q552X, A559T, 1811+1.6kb A>G, 1812-1 G>A, 1898+1 G>T, 1898+1 G>C, 1898+5G>T, P574H, 1949del84, 2043delG, 2055del9>A, 2105del13ins5, 2108delA, 2143delT, 2183_2184delAAinsG, 2184insA, R709X, K710X, 2307insA, R764X, Q890X, 2869insG, 3171delC, 3199del6, R1066C, W1089X (TGG>TAG), Y1092X (C>G), Y1092X (C>A), M1101K, M1101R, D1152H, R1158X, 3667del4, S1196X, W1204X (TGG>TAG), 3791delC, Q1238X, 3876delA, S1251N, S1255X, 3905insT and 4016insT. Poly T determination and confirmatory testing of homozygous results are performed as reflex tests when appropriate.(Farkas DH, Miltgen NE, Stoerker J, et al: The suitability of matrix assisted laser desorption/ionization time of flight mass spectrometry in a laboratory developed test using cystic fibrosis carrier screening as a model. J Molec Diagn. 2010;12:611-619. doi: 10.2353/jmoldx.2010.090233)
Batched, performed most weekdays
81220-CFTR
88240-Cryopreservation (if appropriate)
88235-Amniotic fluid culture (if appropriate)
81265-Maternal cell contamination (if appropriate)