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.

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