Test Catalog

Test Id : CFSMN

Cystic Fibrosis and Spinal Muscular Atrophy Carrier Screen Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Reproductive risk refinement via carrier screening for individuals in the general population for cystic fibrosis and spinal muscular atrophy.

 

Reproductive risk refinement via carrier screening for individuals with a family history of cystic fibrosis and/or spinal muscular atrophy when familial variants are not available

 

This test is not useful for clinical diagnosis of an affected individual.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes targeted testing to evaluate over 500 genes including the 23 cystic fibrosis transmembrane conductance regulator (CFTR) variants recommended by the American College of Medical Genetics and Genomics as well as targeted testing of survival motor neuron 1 (SMN1) and SMN2.

Highlights

A targeted genotyping array is utilized to detect over 500 genetic targets associated with cystic fibrosis or cystic fibrosis-related disorder for the purpose of carrier screening.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Targeted Genotyping Array

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CF and SMA Carrier Screen Panel

Aliases
Lists additional common names for a test, as an aid in searching

CFSMN

Small Carrier Screen

Carrier Screen

Carrier Screening with CF

Carrier Screening with Cystic Fibrosis

Carrier Screening with SMA

Carrier Screening with Spinal Muscular Atrophy

Limited Carrier Screen

Focused Panel

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

This test is specifically for carrier screening purposes and is not intended for diagnostic purposes. For diagnostic testing, order CFMP / Cystic Fibrosis, CFTR Gene, Variant Panel, Varies.

 

If the reproductive partner is also having this test performed, call the lab for a revised risk assessment.

 

Targeted testing for familial variants (also called site-specific or known mutation testing) is available for all genes on this panel under FMTT / Familial Mutation, Targeted Testing, Varies. Call 800-533-1710 to obtain more information about this testing option.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Necessary Information

If there is a family history of cystic fibrosis (CF) or spinal muscular atrophy (SMA), the known genetic variant in the family should be supplied for best interpretation of results.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Specimen Type: Whole blood

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.

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521)  

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
Frozen
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Reproductive risk refinement via carrier screening for individuals in the general population for cystic fibrosis and spinal muscular atrophy.

 

Reproductive risk refinement via carrier screening for individuals with a family history of cystic fibrosis and/or spinal muscular atrophy when familial variants are not available

 

This test is not useful for clinical diagnosis of an affected individual.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes targeted testing to evaluate over 500 genes including the 23 cystic fibrosis transmembrane conductance regulator (CFTR) variants recommended by the American College of Medical Genetics and Genomics as well as targeted testing of survival motor neuron 1 (SMN1) and SMN2.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Because an individual can be a carrier for an autosomal recessive condition without showing signs or symptoms, there is often no family history of such disorders. Therefore, without a family history, a reproductive couple may not know if they have an increased risk to have a child with any given genetic disorder. Carrier screening either before or during a pregnancy can help a reproductive couple further understand their risk to have a child with a genetic condition.

 

Carrier screening for genetic variants associated with cystic fibrosis (CF) and spinal muscular atrophy (SMA) are considered standard of care by American College of Obstetricians and Gynecologists (ACOG) and American College of Medical Genetics and Genomics (ACMG) for all couples regardless of ancestry.(1,2)

 

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 genetic variant detection rate for the variant screening assay. To date, over 1500 variants have been described within the gene that causes CF, 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 the North American population of Northern European descent. Most of the remaining variants are rare, although some show a relatively higher prevalence in certain ethnic groups or in certain atypical presentations of CF such as congenital bilateral absence of the vas deferens (CBAVD). Genetic variants detected by this assay include the 23 variants recommended by the ACMG as well as over 450 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 a select subset of variants.

 

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*

European American

1/25

94%

Ashkenazi Jewish

1/25

95%

African American 

1/65

87%

Hispanic American

1/46

87%

Asian American**

1/90

65%

General US population

1/35

86%

 

*Rates are for classic CF. Rates are lower for atypical forms of CF and for CBAVD.

**Does not apply to individuals of Japanese ancestry.

 

Spinal Muscular Atrophy:

SMA is an autosomal recessive neuromuscular disorder characterized by motor neuron degeneration leading to muscular atrophy with progressive paralysis. It is a genetically complex condition that is traditionally divided into 5 subtypes, depending on the age at which symptoms present and the motor milestones that are achieved. Presentation can range from in utero joint contractures and lack of fetal movement (type 0), to loss of ambulation in adolescence or adulthood (type IV). All patients with SMA develop symmetrical loss of muscle control, most commonly affecting proximal muscles. 

 

The most common form of SMA is associated with the loss of survival motor neuron (SMN) protein, which is encoded by 2 or more genes on chromosome 5. The majority of SMN protein is expressed by the SMN1 gene but a small portion of SMN is also contributed by the SMN2 gene. In fact, SMN1 produces more than 90% of SMN protein, while SMN2 produces about less than 10% of residual SMN protein. This occurs because SMN2 differs from SMN1 by 5 nucleotide changes, one of which leads to alternative exon 7 splicing, and a reduction of SMN2 expression. Most individuals have 2 copies of SMN1, but individuals with as many as 5 copies of SMN1 have been observed. In addition, individuals may also have 0 to 5 copies of SMN2.

 

SMA is most commonly caused by a homozygous deletion of exon 7 in SMN1. However, some patients with this disorder may be compound heterozygotes, with a deletion of one copy of SMN1 and a point alteration in the other allele. The severity of a patient's disease is associated with the number of copies of SMN2 that are present, and 3 or more SMN2 copies are associated with a milder SMA phenotype.

 

As this test is a quantitative assay for the number of SMN1 exon 7 deletions, any result showing 2 SMN1 copies may, in fact, have 2 normal copies of SMN1 in cis (on the same chromosome) and a copy of SMN1 with the exon 7 deletion on the other chromosome (in trans). This is called the "2+0" carrier genotype. The frequency of the "2+0" carrier genotype differs by ancestry. Previously, it was not possible to distinguish a "2+0" carrier from an individual with one copy of SMN1 on each chromosome. However, following a study performed by Luo et al,(3) it is now possible to provide an adjusted genetic residual carrier risk specific to one's ancestry, based on the presence or absence of the SMN1 polymorphism g.27134T>G. The presence of this polymorphism is linked to being a "2+0" carrier in the Ashkenazi Jewish and Asian populations, and it increases the chances that one is a "2+0" carrier in other populations. See the table below for details.

 

Table. SMA carrier residual risk estimates.(3)

Ancestry

Carrier frequency

Detection rate based on copy number alone

Residual risk after detection of 2 copies of SMN1

Detection rate with addition of SMN1 g.27134T>G

Residual risk of being a 2+0 carrier after absence of SMN1 g.27134T>G

Residual risk of being a 2+0 carrier after presence of SMN1 g.27134T>G

 European descent

1/35

95%

1/632

N/A

1/769

1/28

Ashkenazi Jewish

1/41

90%

1/345

94%

1/580

2+0 Carrier

Asian

1/53

92%

1/628

93%

1/701

2+0 Carrier

African American

1/66

71%

1/121

N/A

1/395

1/33

Latinx

1/117

90%

1/1061

N/A

1/1762

1/139

General population

1/54

90%

1/536

N/A

N/A

N/A

 

For details regarding the specific variants identified by this test see Targeted Variants Detected by Focused Carrier Screening Tests.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(4) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A negative result does not eliminate the risk of carrier status for any of the included conditions, due to the possibility that the patient carries a variant that is not interrogated with this assay or the rare chance of a false-negative result for a tested variant. For tested variants, the negative predictive value of this screen is greater than 98%. The patient's residual risk to be a carrier after a negative screen is dependent on ethnic background and family history.

 

A positive control was not available for all variants targeted on this panel. For more information regarding availability of a positive control for each variant see Targeted Variants Detected by Focused Carrier Screening Tests. The negative predictive value of these targets is unknown.

 

Rare variants (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.

 

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(4) This assay was designed to specifically target known pathogenic or likely pathogenic variants. In rare cases, DNA variants of undetermined significance may be identified. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Multiple in-silico evaluation tools may have been used to assist in the interpretation of these results. Of note, the sensitivity and specificity of these tools for the determination of pathogenicity is currently unvalidated.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Bone Marrow transplants from allogenic donors will interfere with testing. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

An online research opportunity called GenomeConnect (genomeconnect.org), a project of ClinGen, is available for the recipient of this genetic test. This patient registry collects deidentified genetic and health information to advance the knowledge of genetic variants. Mayo Clinic is a collaborator of ClinGen. This may not be applicable for all tests.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Langfelder-Schwind E, Karczeski B, Strecker MN, 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. doi: 10.1007/s10897-013-9636-9

2. Sugarman EA, Nagan N, Zhu H, et al: Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012;20(1):27-32. doi: 10.1038/ejhg.2011.134

3. Luo M, Liu L, Peter I, et al: An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 2014;16:149-156. doi: 10.1038/gim.2013.84

4. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424. doi: 10.1038/gim.2015.30

 5. Carrier Testing for Cystic Fibrosis. Cystic Fibrosis Foundation; Accessed May 24, 2021. Available at www.cff.org/What-is-CF/Testing/Carrier-Testing-for-Cystic-Fibrosis/

6. 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

7. Prior TW, Professional Practice and Guidelines Committee: Carrier screening for spinal muscular atrophy. Genet Med. 2008;10:840-842. doi: 10.1097/GIM.0b013e318188d069

9: Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol. 2017 Mar;129(3):e41-e55. doi: 10.1097/AOG.0000000000001952

10: Gregg AR, Aarabi M, Klugman S, et al; ACMG Professional Practice and Guidelines Committee: Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 Oct;23(10):1793-1806. doi: 10.1038/s41436-021-01203-z. Erratum in: Genet Med. 2021 Aug 27

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

The targeted genotyping array utilizing the ThermoFisher GeneTitan platform is used to detect select genetic variants in the following genes associated with heritable conditions: cystic fibrosis transmembrane conductance regulator (CFTR) and survival motor neuron 1 (SMN1). SMN2 may be reported in conjunction with relevant genotype findings.

 

For details regarding the targeted mutations identified by this test see Targeted Variants Detected by Focused Carrier Screening Tests.

 

Multiplex ligation-dependent probe amplification, polymerase chain reaction (PCR), relative quantitative PCR, droplet digital PCR, and Sanger sequencing are used to confirm alterations detected by microarray when appropriate.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Thursday, Sunday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

7 to 21 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81220

81329

81222

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
CFSMN CF and SMA Carrier Screen Panel 98039-1
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
608350 Result Summary 50397-9
608351 Result 82939-0
608352 Interpretation 69047-9
608353 Additional Information 48767-8
608354 Method 85069-3
608355 Specimen 31208-2
608356 Source 31208-2
608357 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports