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  • Test code: 03240
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Hereditary Motor Neuropathy Panel

Test description

The Invitae Hereditary Motor Neuropathy Panel analyzes genes that are associated with hereditary motor neuropathies (HMNs) a clinically and genetically heterogeneous group of conditions characterized by loss of motor neurons within the spinal cord resulting in weakness and muscle wasting; in some cases, HMNs are referred to as spinal muscular atrophies (SMAs). These genes were curated based on currently available evidence to provide a comprehensive test for the genetic causes of HMN. Given that HMNs are a heterogeneous group of conditions, identification of the underlying genetic cause can help confirm a clinical diagnosis, predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.

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Primary panel (27 genes)

ASAH1 ATP7A BICD2 BSCL2 CHCHD10 DCTN1 DNAJB2 DYNC1H1 EXOSC9 FBXO38 GARS HEXA HINT1 HSPB1 HSPB8 IGHMBP2 MORC2 PLEKHG5 REEP1 SIGMAR1 SLC5A7 SMN1, SMN2 TRPV4 UBA1 VAPB VRK1

Add-on Preliminary-evidence Genes for Hereditary Motor Neuropathy (3 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future.

HSPB3 LAS1L SLC25A21

Alternative tests to consider

Broad disorders tested:

  • Hereditary Motor Neuropathy
  • Spinal Muscular Atrophy

Individual disorders tested:

  • ATP7A-related distal hereditary motor neuropathy
  • distal hereditary motor neuropathy 2A (HMN2A)
  • distal hereditary motor neuropathy 2B (HMN2B)
  • distal hereditary motor neuropathy 2D (HMN2D)
  • distal hereditary motor neuropathy 5 (HMN5)
  • distal hereditary motor neuropathy 5B (HMN5B)
  • distal hereditary motor neuropathy 6 (HMN6), spinal muscular atrophy with respiratory distress 1 (SMARD1)
  • distal hereditary motor neuropathy 7 (HMN7A)
  • distal hereditary motor neuropathy 8 (HMN8), scapuloperoneal spinal muscular atrophy (SPSMA)
  • distal hereditary motor neuropathy type VIIB (HMN7B)
  • distal spinal muscular atrophy 2 (DSMA2)
  • distal spinal muscular atrophy 4 (DSMA4)
  • distal spinal muscular atrophy 5 (DSMA5)
  • late-onset spinal muscular atrophy, Finkel type (SMAFK)
  • lower extremity predominant spinal muscular atrophy 1 (SMALED1)
  • neuromyotonia and axonal neuropathy (NMAN)
  • polyarticular arthritis and spinal muscular atrophy, spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME), Jankovic Rivera syndrome
  • pontocerebellar hypoplasia type 1D (PCH1D)
  • spinal muscular atrophy (SMA)
  • spinal muscular atrophy 2 (SMAX2)
  • spinal muscular atrophy with or without pontocerebellar hypoplasia type 1A (PCH1A)
  • spinal muscular atrophy, Jokela type (SMAJ)
  • spinal muscular atrophy, lower extremity predominant 2 (SMALED2)
  • Tay-Sachs disease, beta-hexosaminidase A (HEXA) deficiency

To view the complete clinical description of this panel, click here.

Hereditary motor neuropathy can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ASAH1 NM_177924.3
ATP7A NM_000052.6
BICD2 NM_001003800.1
BSCL2 NM_032667.6
CHCHD10 NM_213720.2
DCTN1 NM_004082.4
DNAJB2 NM_001039550.1
DYNC1H1 NM_001376.4
EXOSC9 NM_001034194.1
FBXO38 NM_030793.4
GARS NM_002047.2
HEXA NM_000520.4
HINT1 NM_005340.6
HSPB1 NM_001540.3
HSPB3 NM_006308.2
HSPB8 NM_014365.2
IGHMBP2 NM_002180.2
LAS1L NM_031206.4
MORC2 NM_001303256.2
PLEKHG5 NM_020631.4
REEP1 NM_022912.2
SIGMAR1 NM_005866.3
SLC25A21 NM_030631.3
SLC5A7 NM_021815.2
SMN1, SMN2* NM_000344.3; NM_017411.3
TRPV4 NM_021625.4
UBA1 NM_003334.3
VAPB NM_004738.4
VRK1 NM_003384.2

SMN1 or SMN2: The SMN1 gene is identical to the SMN2 gene with the exception of exon 8 (typically referred to as exon 7). This assay unambiguously detects SMN1 exon 8 copy number and sequence variants. Sequence variants outside of exon 8 will also be detected, but this assay cannot determine whether the variant is located in SMN1 or SMN2. SMN2 exon 8 copy number will be reported for individuals with a positive result in SMN1. CNVs of exons 1-7 of SMN1 or SMN2 (typically referred to as exons 1-6 in the literature) will not be reported. Variants in all exons with no evidence towards pathogenicity are not reported, but are available upon request. This assay cannot 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). The SMA-STAT test does not detect sequence variants in SMN1 or SMN2, and therefore cannot be used to identify compound heterozygotes.