Test Catalog

Test Id : SMN1Z

SMN1 Gene, Full Gene Analysis, Varies

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

Confirming a diagnosis of spinal muscular atrophy due to nucleotide variants in SMN1 gene

 

Second-tier carrier screening when there is a family history of spinal muscular atrophy, but an affected individual is not available for testing, or when disease-causing variants are unknown

 

Second-tier carrier screening for the reproductive partner of a known SMA carrier

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

Testing includes full gene sequencing of the SMN1 gene.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.

 

See Inherited Motor Neuron Disease Testing Algorithm in Special Instructions.

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

Polymerase Chain Reaction (PCR) followed by DNA Sequencing

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

SMN1 Full Gene Analysis

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

Spinal Muscular Atrophy Type I

SMA1

SMAI

SMA Infantile Acute Form

Muscular Atrophy, Infantile

Severe Infantile Acute Spinal Muscular Atrophy

Spinal Muscular Atrophy-1

Spinal Muscular Atrophy, Type II

SMA2

SMAII

Muscular Atrophy, Spinal, Intermediate Type

Muscular Atrophy, Spinal, Infantile Chronic Form

Infantile Chronic Spinal Muscular Atrophy

Spinal Muscular Atrophy-2

Spinal Muscular Atrophy, Type III

SMA3

SMAIII

Muscular Atrophy, Juvenile

Kugelberg-Welander Syndrome

KWS

Spinal Muscular Atrophy, Mild Childhood and Adolescent Form

Spinal Muscular Atrophy-3

Spinal Muscular Atrophy, Type IV

SMA4

SMAIV

Spinal Muscular Atrophy, Adult Form

Spinal Muscular Atrophy, Proximal, Adult, Autosomal Recessive

Adult-Onset SMA

Spinal Muscular Atrophy-4

SMN1Z

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.

 

See Inherited Motor Neuron Disease Testing Algorithm in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

This is not the preferred genetic test for carrier screening or diagnosis in individuals with suspicion of spinal muscular atrophy (SMA). For these situations, order SMNCS / Spinal Muscular Atrophy Carrier Screening, Deletion/Duplication Analysis, Varies or SMNDX / Spinal Muscular Atrophy Diagnostic Assay, Deletion/Duplication Analysis, Varies.

 

This test is appropriate for second-tier carrier screening following SMNCS / Spinal Muscular Atrophy Carrier Screening, Deletion/Duplication Analysis, Varies when:

-There is a family history of SMA, but an affected individual is not available for testing

-The disease-causing variants are unknown

-Testing the reproductive partner of a known SMA carrier

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

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

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: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Supplies: Fibroblast Biopsy Transport Media (T115)

Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Supplies: Card - Blood Spot Collection (Filter Paper) (T493)

Specimen Type: Blood spot

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card

Specimen Volume: 5 Blood spots on collection card

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 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 in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.

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 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.

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

Blood: 1 mL

Blood Spots: 3 punches 3-mm diameter

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 Varies (preferred)

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

Confirming a diagnosis of spinal muscular atrophy due to nucleotide variants in SMN1 gene

 

Second-tier carrier screening when there is a family history of spinal muscular atrophy, but an affected individual is not available for testing, or when disease-causing variants are unknown

 

Second-tier carrier screening for the reproductive partner of a known SMA carrier

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

Testing includes full gene sequencing of the SMN1 gene.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.

 

See Inherited Motor Neuron Disease Testing Algorithm in Special Instructions.

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

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 American College of Medical Genetics and Genomics (ACMG) recommends offering SMA carrier screening to all couples, regardless of race or ethnicity, before conception or early in pregnancy.

 

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 survival motor neuron 1 (SMN1) gene, but a small portion of SMN is also contributed by the survival motor neuron 2 (SMN2) gene. Indeed, SMN1 produces more than 90% of SMN protein, while SMN2 produces less than 10% of residual SMN protein. This occurs because SMN2 differs from SMN1 by 5 nucleotides, 1 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 are detected. 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 1 copy of SMN1 and a nucleotide variant in the other allele. The severity of a patient's disease course 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.

 

This test aims to specifically identify nucleotide variants in SMN1 by direct sequencing and to distinguish these nucleotide variants from changes within SMN2. However, SMN1 exon 1 variants are still unable to be distinguished from changes within SMN2 exon 1.

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 alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) 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

Variants detected in SMN1 exon 1 cannot be distinguished from variants inSMN2 exon 1. Therefore, additional molecular analyses are required to confirm results in this region.

 

A small percentage of individuals who are carriers or have a diagnosis of spinal muscular atrophy may have a variant that is not identified by this method (eg, large genomic deletions, promoter alterations). The absence of a variant, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of spinal muscular atrophy. For carrier testing, it is important to first document the presence of an SMN1 gene variant in an affected family member.

 

In some cases, DNA alterations of undetermined significance may be identified.

 

Rare alterations 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.

 

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.

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

1. 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

2. Wirth B: An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat. 2000;15:228-237

3. Clermont O, Burlet P, Benit P, et al: Molecular analysis of SMA patients without homozygous SMN1 deletions using a new strategy for identification of SMN1 subtle mutations. Hum Mutat. 2004;24:417-427

4. Kubo Y, Nishio H, Saito K: A new method for SMN1 and hybrid SMN gene analysis in spinal muscular atrophy using long-range PCR followed by sequencing. J Hum Genet. 2015;60: 233-239

5. Prior T, Leach ME, Finanger E: Spinal muscular atrophy. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. Gene Reviews [Internet]. University of Washington, Seattle; 2000. Updated November 14, 2019. Accessed September 28, 2020. Available at www.ncbi.nlm.nih.gov/sites/books/NBK1352/

6. The Human Gene Mutation Database (HGMD), Professional version 2017.2 from BIOBASE. A database of germline mutations in genes associated with human inherited disease. Accessed Sep 12, 2017. Available at https://portal.biobase-international.com/hgmd/pro/start.php

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

Long-range-PCR of SMN1 exons 2-8, followed by bidirectional Sanger sequence analysis for nucleotide variants in all protein-coding regions and intron/exon boundaries of SMN1. SMN1 exon 1 is PCR-amplified and bidirectionally Sanger-sequenced.(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.

Varies

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.

14 to 20 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.

81336

88233-Tissue culture, skin, or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

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