Cystic Fibrosis Testing

Cystic fibrosis (CF) affects approximately 30,000 children and adults in the US, and about 10 million Americans are carriers for the condition. Ambry Genetics is committed to caregivers and patients in the CF community through diagnostic testing, research, education, and support for advocacy groups.


Cystic fibrosis (CF) affects approximately 30,000 children and adults in the US, and about 10 million Americans are carriers for the condition. Ambry Genetics is committed to caregivers and patients in the CF community through diagnostic testing, research, education, and support for advocacy groups.

Founded in 1999, Ambry Genetics was the first commercial laboratory to offer clinical genetic testing for cystic fibrosis using gene sequencing technology.  Since then, Ambry has analyzed the complete CF gene (CFTR) for more than 35,000 patients. As a result, Ambry has the most robust single-laboratory database in the world from which to accurately and carefully interpret patient results.  Due to CFTR’s large size and the wide genetic heterogeneity seen in CF, this powerful database is highly valuable to clinicians.

Ambry has developed a range of genetic testing options to meet a variety of clinical needs.
CFTR sequencing and deletion/duplication analysis is the most comprehensive test available, detecting ~99% of disease-causing CFTR changes (or mutations), including gross deletions and duplications. Testing begins with CFTR full sequence analysis, which detects 97-98% of mutations. If two pathogenic or likely pathogenic genetic alterations are found in a symptomatic patient, or if one is found on a carrier screen in a patient without symptoms, results are presumed to be informative and no further analysis is performed. If results are not informative or if clinical suspicion for CF remains, testing proceeds to gross deletion/duplication analysis.  These options may also be run concurrently.  

CFTR sequencing and deletion/duplication analysis may be optimal for:

  • Confirming a diagnosis in patients known or suspected to have CF
  • Testing newborns found to have a single CFTR mutation on a newborn screen
  • Carrier testing for high-risk individuals and partners of CF carriers

CF 102 is a screening panel of >100 CFTR disease-causing mutations carefully selected to provide the highest overall mutation detection rate (91%) of any screening option. This test includes the 23 mutations defined as “common mutations” by the American College of Medical Genetics and Genomics (ACMG). CF 102 offers a high analytic sensitivity, with a quick turnaround time and low cost.

CF 102 may be optimal for:

  • Confirming a diagnosis in patients known or suspected to have CF
  • Carrier screening for relatives of those with CF
  • Carrier testing for those with a family history of known CFTR mutations
  • Meeting the American Congress of Obstetrics and Gynecologists’ (ACOG’s) and the National Society of  Genetic  Counselors’ (NSGC’s) CF carrier screening recommendations1,2

CF 102 White Paper

508 FIRST provides a quick and cost-effective screen for deltaF508, the most common CFTR mutation.  This test analyzes the deltaF508 mutation first, with a potential reflex to full gene sequence analysis and deletion/duplication analysis, if necessary.

508 FIRST may be optimal for:

  • Confirming a diagnosis in those with classic characteristics of CF, but no previous genetic testing 

508 ONLY provides analysis of only the deltaF508 mutation. 

508 ONLY may be optimal for:

  • Those with a known family history of CF that is due to the delta F508 mutation

Ambry also offers Specific Site Analysis (SSA) for known familial CFTR mutations or alterations.  When analysis of a specific mutation or alteration in the CFTR gene is requested, sequencing of the specific region can be performed.

Disease Name 
Cystic fibrosis
Disease Information 

Cystic fibrosis (CF) is a relatively common genetic condition that affects about 30,000 children and adults in the United States.1  About 1 in 25 non-Hispanic Caucasians is a CF carrier, and this frequency is typically lower in other ethnic groups.2

CF is caused by mutations in the CFTR gene; this gene codes for the cystic fibrosis transmembrane conductance regulator.  CF runs through families in an autosomal recessive inheritance pattern.  People with the most common type of CF have two CFTR gene mutations, which usually cause the body to produce very thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. People with CF have persistent coughing, wheezing or shortness of breath.  Thick mucus secretions can also obstruct the pancreas and prevent natural digestive enzymes from reaching the intestines to help break down and absorb food.  This can cause pancreatitis, pancreatic insufficiency, and poor weight gain.  10-15% of newborns with CF have meconium ileus found at birth.3  In addition, babies with echogenic bowel on ultrasound have a higher risk of having CF (the risks increase as the degree of echogenicity increases).4

People with CF often have other symptoms including high sweat chloride levels, chronic sinus disease, and an excessive appetite but low weight gain.  CFTR mutations may also lead to congenital absence of the vas deferens (CAVD) and infertility in males, who may not have pulmonary or gastrointestinal symptoms of CF.3  Exact symptoms can vary widely between people with CF, and more is being learned every day – for those with CF and those who are CF carriers – through ongoing research and clinical trials.  This variability in symptoms is, in part, due to the large size of the CFTR gene and the more than 1,900 different CFTR mutations and variants described to date.5

Treatment/prevention of complications may be implemented if a diagnosis is suspected or confirmed, and these treatments can involve many organ systems.  In addition, regularly scheduled visits to CF care providers (if available) for ongoing surveillance and management are critical for those with the condition.

Testing Benefits & Indication 

Genetic testing for CF may be offered for:

  • Confirming a diagnosis of CF in individuals with a known or suspected diagnosis based on symptoms.  An early diagnosis directly impacts medical management and allows implementation of treatment in a timely manner to optimize care for a patient.
  • Those at increased risk to be a carrier based on ethnicity, specific symptoms, family history, and/or for partners of individuals that are CF carriers (for reproductive/prenatal genetic testing purposes). 
  • Confirming a diagnosis in pregnancies identified to be at increased risk for CF (e.g. echogenic bowel, other indicators).
Test Description 
  (Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified by agarose gel electrophoresis)
Specific Site Analysis (SSA) Traditional Sanger dideoxy terminator DNA sequencing and/or MLPA are used if testing for specific mutation(s) in the CFTR gene (other than deltaF508) is requested
CFTR Sequencing and Deletion/Duplication CFTR full-gene sequence analysis is performed using next generation sequencing (NGS). The analytical range includes: exons 1 to 27, as well as at least 20 bases into the 5’- and 3’-ends of all introns, 5’- and 3’-untranslated regions (5’UTR and 3’UTR). This assay is also capable of assessing the poly-T tract within intron 10 and identifying the c.1679+1634A>G (c.1811+1634A>G or c.1811+1.6kb) mutation in intron 12 and the c.3717+12191C>T (c.3849+10kbC>T) mutation in intron 22. Test includes full-gene sequence analysis plus reflexing to gross deletion/duplication. Gene deletion/duplication analysis is performed using Multiplex Ligation-dependent Probe Amplification (MLPA, MRC Holland). Gross deletion/duplication analysis determines gene copy number for any of the 27 exons.
CF 102 Detection of the following specific mutations in the CFTR gene:
  1078delT (c.948delT)
1154insTC (c.1022_1023insTC)
1248+1G>A (c.1116+1G>A)
1288insTA (c.1153_1154insAT)
1471delA (c.1340delA)
1717-1G>A (c.1585-1G>A)
1898+1 G>A (c.1766+1G>A )
1898+3A>G (c.1766+3A>G )
1949del84 (c.1817_1900del84)
2055del9>A (c.1923_1931del9insA)
2143delT (c.2012delT)
2183AA>G (c.2051_2052delAAinsG)
2184delA (c.2052delA)
2184insA (c.2052insA)
2307insA (c.2175_2176insA)
2347delG (c.2215delG)
2585delT (c.2453delT)
2622+1G>A (c.2490+1G>A)
2789+2insA (c.2657+2_2657+3insA)
2789+5G>A (c.2657+5G>A)
3120+1G>A (c.2988+1G>A)
3120G>A (c.2988G>A)
3199del6 (c.3067_3072delATAGTG)
3272-26A>G (c.3140-26A>G)
3600G>A (c.3468G>A)
3659delC (c.3528delC)
3849+10kbC>T (c.3717+12191C>T)
3876delA (c.3744delA)
3905insT (c.3773_3774insT)
394delTT (c.262_263delTT)
4005+2T>C (c.3873+2T>C)
405+1G>A (c.273+1G>A)
406-1G>A (c.274-1G>A)
4209TGTT>AA (c.4077_4080delTGT- TinsAA)
621+1G>T (c.489+1G>T)
663delT (c.531delT)
711+1G>T (c.579+1G>T)
935delA (c.803delA)
p.A455E (c.1364C>A)
p.D1152H (c.3454G>C)
p.E116K (c.346G>A)
p.E1371X (c.4111G>T)
p.E384X (c.1150G>T)
p.E585X (c.1753G>T)
p.E60X (c.178G>T)
p.E92X (c.274G>T)
p.G1061R (c.3181G>C)
p.G1244E (c.3731G>A)
p.G178R (c.532G>A)
p.G330X (c.988G>T)
p.G480C (c.1438G>T)
p.G542X (c.1624G>T)
p.G551D (c.1652G>A)
p.G551S (c.1651G>A)
p.G85E (c.254G>A)
EX2del, EX2_3del
deltaF508 (c.1521_1523delCTT)
deltaI507 (c.1519_1521delATC)
p.L1077P (c.3230T>C)
p.L467P (c.1400T>C)
p.M1101K (c.3302T>A)
p.N1303K (c.3909C>G)
p.P67L (c.200C>T)
p.Q1042X (c.3124C>T)
p.Q220X (c.658C>T)
p.Q414X (c.1240C>T)
p.Q493X (c.1477C>T)
p.Q552X (c.1654C>T)
p.Q98R (c.293A>G)
p.Q98X (c.292C>T)
p.R1066C (c.3196C>T)
p.R1066H (c.3197G>A)
p.R1070W (c.3208C>T)
p.R1158X (c.3472C>T)
p.R1162X (c.3484C>T)
p.R117C (c.349C>T)
p.R117H (c.350G>A)
p.R334Q (c.1001G>A)
p.R334W (c.1000C>T)
p.R347H (c.1040G>A)
p.R347P (c.1040G>C)
p.R553X (c.1657C>T)
p.R560T (c.1679G>C)
p.R709X (c.2125C>T)
p.R75X (c.223C>T)
p.R764X (c.2290C>T)
p.S1196X (c.3587C>G)
p.S1251N (c.3752G>A)
p.S466X (c.1397C>G and c.1397C>A)
p.S489X (c.1466C>A)
p.S549N (c.1646G>A)
p.S912X (c.2735C>A)
p.S945L (c.2834C>T)
p.T338I (c.1013C>T)
p.T351I (c.1052C>T)
p.V520F (1558G>T)
p.W1089X (c.3266G>A)
p.W1204X (c.3612G>A)
p.W1282X (c.3846G>A)
p.Y1032C (c.3095A>G)
p.Y1092X (c.3276C>A)
p.Y563N (c.1687T>A)
if p.R117H is detected, then reflex poly T / TG repeat analysis is performed.
*Novel variants are always reported. Polymorphisms and the poly T status will be reported upon request. The following sites are used to search for previously described CF mutations and polymorphisms: Toronto Sick Children’s CF database, HGMD, CFTR2, and online search engines (i.e., PubMed). Sequence analysis is based on the following NCBI reference sequence: NM_000492.

Special Notes:
Poly T and TG tract results will be included on the report in the following situations:

For sequencing:
a. The “Report PolyT / TG Status” box is checked on the Test Requisition Form
b. Anytime a 5T is found, TG status will automatically be reported

For screening panels:
a. The “Report PolyT / TG Status” box is checked on the Test Requisition Form (additional cost)
b. The R117H mutation is detected (no additional cost) 

CF Carrier Risks and CFTR Mutation/Alteration Detection Rates[6]
  Individuals with CF and
Ethnic Group Estimated Detection Rate*** Before Tests Carrier Risk** After Negative Test No CF Mutations One CF Mutation
CF Gene Sequence CF Gene Sequence and Del/Dup CF Gene Sequence CF Gene Sequence and Del/Dup CF Gene Sequence and Del/Dup
Ashkenazi Jewish 97%-98% ~99% 1/24 ~1 in 959 ~1 in 2301 ~0.01% ~2%
Non-Hispanic Caucasian 97-98% ~99% 1/25 ~1 in 1001 ~1 in 2401 ~0.01% ~2%
African American 97-98% ~99% 1/61 ~1 in 2501 ~1 in 6001 ~0.01% ~2%
Hispanic American * 97-98% ~99% 1/58 ~1 in 2376 ~1 in 5701 ~0.01% ~2%
Asian American 97-98% ~99% 1/94 ~1 in 3876 ~1 in 9301 ~0.01% ~2%

* This is a pooled set of data and requires additional information to predict risk accurately for specific Hispanic populations.
** Based on a negative family history.
*** Based on Ambry’s empirical data.

Ambry in the Field

Most recent CFTR Publication:
Replacing CFTR Sanger Sequencing in the Clinical Lab with a Reliable, Targeted Next-Generation Sequencing Assay 

View our CFTR educational webinar recorded on January 22, 2015:
Analyzing Historical Mutations in the CFTR gene Reveals a High Number of Reclassified Variants

View our educational webinar recorded may 26, 2015:
Cystic Fibrosis Newborn Screening: What you need to know

Mauli Ola Foundation

The Mauli Ola Foundation (MOF) was founded in 2007 to promote awareness of genetic disorders, and has a special relationship with the CF community and Ambry Genetics. The Foundation began as a group of surfers that banded together to introduce surfing as a natural treatment for people with CF. MOF raises funds to support programs for those with life-threatening illnesses and provide direct, immediate ways for children with genetic disorders to enjoy healthy lives through natural treatments.

Mauli Ola Surf Experience Days get kids with CF into the ocean (high in saline) with professional surfers to experience what natural therapies can do for their lungs. The saline in the air and water breaks down lung congestion and is a healthy, fun alternative to the typical regimen of medications and other therapies for CF. Since 2007, MOF has taken over 2,000 patients with CF surfing during Surf Experience Days. It has now expanded its reach by adding hospital visits and other activities that touch the lives of children with a variety of health issues.

To learn more about MOF, please visit

Mutation Detection Rate 

Clinical sensitivity for CF genetic screening depends on the test ordered and the ethnic background of the patient.  Gene sequencing and deletion/duplication anaylisis can detect mutations in 99% of people with a clinical diagnosis of CF (clinical sensitivity).  Ambry's cystic fibrosis testing can detect >99.9% of described mutations in the CFTR gene, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Turnaround Time 
1000 CFTR Gene Sequence Analysis 5-13
1002 508 First 5-13
1004 CFTR Deletion/duplication analysis 5-13
1006 CFTR Gene Sequence with reflex to Deletion/Duplication Analysis 5-13
1007 CFTR Gene Sequence and Deletion/Duplication Analysis (concurrent) 5-13
1018 CF102 screening panel 5-13
1008 CFTR specific site analysis (also use for 508 ONLY) 7-14
1010 Poly T/TG repeat analysis 7-14


  1. American Congress (formerly College) of Obstetricians and Gynecologists Committee on Genetics.  ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011 Apr;117(4):1028-31.
  2. Langfelder-Schwind E,  et al.  Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors.  J Genet Couns. 2014 Feb;23(1):5-15. 
  3. Moskowitz SM et al. Clinical practice and genetic counseling for cystic fibrosis and CFTR-related disorders.  Genet Med. 2008 Dec;10(12):851-68. 
  4. Cystic Fibrosis Foundation, Frequently Asked Questions, 2014,
  5. Moskowitz SM et alCFTR-Related Disorders.  GeneReviews 2001, updated 2008. Pagon RA, Adam MP, Ardiner HH et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2014. 
  6. Prach L et al.   Novel CFTR Variants Identified during the First 3 Years of Cystic Fibrosis Newborn Screening in California. J Mol Diagn. 2013 Sep;15(5):710-22.
  7. Ghose I et al.  Hyperechogenic fetal bowel: a prospective analysis of sixty consecutive cases.   BJOG. 2000 Mar;107(3):426-9. 
  8. Rohlfs EM et al.  Cystic Fibrosis Carrier Testing in an Ethnically Diverse US Population, Clin Chem.  2011 Jun;57(6):841-8.