The Invitae Spinal Muscular Atrophy STAT test analyzes the copy number of SMN1, which is known to cause spinal muscular atrophy (SMA). SMA is a neuromuscular disorder caused by the loss of motor neurons within the spinal cord, resulting in progressive muscle weakness and atrophy. SMN2 copy number, which can modify disease severity in individuals with SMN1-related SMA, is reported for individuals with a homozygous deletion of SMN1. This test does not detect SMN1 sequence variants.
This test provides an accelerated 4 day turnaround time (TAT), which can facilitate urgent management and treatment decisions. Identification of homozygous deletion of SMN1 combined with the determination of SMN2 copy number is a predictor of disease severity and identifies those that would benefit from new and emerging therapies. Early intervention is critical to modulate the progressive degeneration seen in SMA.
This test analyzes SMN1 and SMN2 copy number but does not detect SMN1 sequence variants, which are found in 2-5% of individuals affected with SMA. If there is reason to suspect a patient carries a sequence variant, the Invitae Spinal Muscular Atrophy Panel should be considered instead:
SMN1 and SMN2 can also be ordered as a part of a broader panel. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate:
Please note that re-requisitions to other neuromuscular panels is not available for SMA STAT panel orders. Any additional test requisitions will require an additional sample and billing event.
Spinal muscular atrophy is inherited in an autosomal recessive pattern.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory.
This test determines SMN1 and SMN2 exon 8 copy number by Droplet Digital PCR (ddPCR). Due to sequence similarity between SMN1 and SMN2, the copy number of exon 8 is used to infer the copy number of the entire gene. The ddPCR method is based on partitioning a PCR reaction with primers and probes for SMN1/2 and a copy number reference into 20,000 individual droplets, thermocycling, then measuring the endpoint fluorescence intensity of each droplet. The instrument software provides a count of the number of droplets for each genotype and generates an absolute count of the number of copies of each target in the reaction and thus the copy number. Use of ddPCR for both copy number and single-base discrimination is a well-established technology supported by commercial reagents, instrumentation, and analytical tools. Reported variants are not confirmed by an orthogonal technology.
Based on validation study results, this assay achieves >98.5% analytical sensitivity and specificity for SMN1 and SMN2 exon 8 deletions. Mosaic copy-number deletions and duplications may not be detected. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases (such as circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion, or maternal cell contamination), the analyzed DNA may not represent the patient’s constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
|SMN1, SMN2*||SMN1: NM_000344.3, SMN2: NM_017411.3|
SMN1 (SMA-STAT-TAT): SMN1, SMN2: The SMN1 gene is identical to the SMN2 gene with the exception of exon 8 (also known as exon 7). This assay detects SMN1 and SMN2 exon 8 copy number, which is used to infer the copy number of the entire SMN1 gene. SMN2 exon 8 copy number is only reported for individuals with a homozygous deletion of SMN1 exon 8. This test does not detect sequence variants in SMN1 or SMN2, and therefore cannot be used to identify compound heterozygotes. This test also does not detect silent carriers (individuals that have 2 functional copies of SMN1 on one chromosome and zero copies on the other). Therefore a negative result for carrier testing greatly reduces but does not eliminate the chance that a person is a carrier. For individuals with 2 copies of SMN1, the residual risk of being a carrier has been reported to be 1 in 121 in African Americans, 1 in 345 in Ashkenazi Jewish individuals, 1 in 628 in Asians, 1 in 632 in Caucasians, and 1 in 1061 in Hispanic individuals (PMID: 23788250).