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  • Test code: 03200
  • 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 Comprehensive Neuropathies Panel

Test description

The Invitae Comprehensive Neuropathies Panel analyzes genes that are associated with hereditary neuropathies, including but not limited to Charcot-Marie-Tooth disease (CMT), hereditary motor neuropathy (HMN), and hereditary sensory and autonomic neuropathy (HSAN). The genetic heterogeneity associated with these conditions can make it difficult to use phenotype as the sole criterion to select a definitive cause. These genes were curated based on the available evidence to date in order to provide analysis for hereditary neuropathies. Given the clinical overlap of hereditary neuropathies, broad panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication. Some genes in this test may also be associated with additional unrelated disorders, which are not included in the list of disorders tested. Genetic testing of these genes may 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 (102 genes)

AARS AIFM1 APOA1 ASAH1 ATL1 ATL3 ATP1A1 ATP7A BAG3 BICD2 BSCL2 CHCHD10 COX6A1 CYP27A1 CYP7B1 DCTN1 DHTKD1 DNAJB2 DNM2 DNMT1 DRP2 DST DYNC1H1 EGR2 ELP1 EXOSC9 FBLN5 FBXO38 FGD4 FIG4 GAN GARS GDAP1 GJB1 GLA GNB4 GSN HARS HEXA HINT1 HMBS HSPB1 HSPB8 IGHMBP2 INF2 KIF1A KIF5A LITAF LMNA LRSAM1 MARS MCM3AP MED25 MFN2 MME MORC2 MPZ MTMR2 NDRG1 NEFH NEFL NGF NTRK1 PDK3 PLEKHG5 PMP2 PMP22 POLG POLG2 PRDM12 PRPS1 PRX RAB7A REEP1 RETREG1 SBF1 SBF2 SCN11A SCN9A SEPT9 SH3TC2 SIGMAR1 SLC12A6 SLC25A46 SLC52A2 SLC52A3 SLC5A7 SMN1, SMN2 SPG11 SPTLC1 SPTLC2 SURF1 TFG TRIM2 TRPV4 TTR UBA1 VAPB VRK1 WNK1 YARS

Add-on Preliminary-evidence Genes for Neuropathies (9 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.

ARHGEF10 CCT5 HSPB3 LAS1L MICAL1 SCN10A SGPL1 SLC25A21 SLC52A1

Broad disorders tested:

  • Charcot-Marie-Tooth Disease
  • Hereditary Motor Neuropathy
  • Hereditary Sensory and Autonomic Neuropathy
  • Small Fiber Neuropathy
  • Riboflavin Transporter Deficiency Neuronopathy
  • Hereditary Transthyretin-Mediated Amyloidosis
  • Spinal Muscular Atrophy

Individual disorders tested:

  • Charcot-Marie-Tooth Disease (CMT) Subtypes
  • BAG3-related Charcot-Marie-Tooth disease
  • Charcot Marie Tooth disease type 2 (CMT2)
  • Charcot-Marie-Tooth disease D (CMTRID)
  • Charcot-Marie-Tooth disease type 1A (CMT1A), type 1E (CMT1E), hereditary neuropathy with liability to pressure palsies (HNPP)
  • Charcot-Marie-Tooth disease type 1B (CMT1B), type 2I (CMT2I), type 2J (CMT2J), dominant intermediate (DI-CMTD)
  • Charcot-Marie-Tooth disease type 1C (CMT1C)
  • Charcot-Marie-Tooth disease type 1D (CMT1D), type 3 (CMT3), Dejerine-Sottas syndrome, type 4E (CMT4E), congenital hypomyelinating neuropathy
  • Charcot-Marie-Tooth disease type 1F (CMT1F), type 2E (CMT2E)
  • Charcot-Marie-Tooth disease type 1G (CMT1G)
  • Charcot-Marie-Tooth disease type 1X (CMT1X)
  • Charcot-Marie-Tooth disease type 2A (CMT2A), type 6A (CMT6A)
  • Charcot-Marie-Tooth disease type 2B (CMT2B)
  • Charcot-Marie-Tooth disease type 2B1 (CMT2B1)
  • Charcot-Marie-Tooth disease type 2C (CMT2C)
  • Charcot-Marie-Tooth disease type 2CC (CMT2CC)
  • Charcot-Marie-Tooth disease type 2D (CMT2D)
  • Charcot-Marie-Tooth disease type 2DD (CMT2DD)
  • Charcot-Marie-Tooth disease type 2F (CMT2F)
  • Charcot-Marie-Tooth disease type 2K (CMT2K), type 4A (CMT4A), recessive intermediate A (CMTRIA)
  • Charcot-Marie-Tooth disease type 2L (CMT2L)
  • Charcot-Marie-Tooth disease type 2M (CMT2M), type B (CMTDIB)
  • Charcot-Marie-Tooth disease type 2N (CMT2N)
  • Charcot-Marie-Tooth disease type 2O (CMT2O)
  • Charcot-Marie-Tooth disease type 2P (CMT2P)
  • Charcot-Marie-Tooth disease type 2Q (CMT2Q)
  • Charcot-Marie-Tooth disease type 2S (CMT2S)
  • Charcot-Marie-Tooth disease type 2T (CMT2T)
  • Charcot-Marie-Tooth disease type 2U (CMT2U)
  • Charcot-Marie-Tooth disease type 2X (CMT2X)
  • Charcot-Marie-Tooth disease type 2Z (CMT2Z)
  • Charcot-Marie-Tooth disease type 4 (CMTX4), Cowchock syndrome
  • Charcot-Marie-Tooth disease type 4B1 (CMT4B1)
  • Charcot-Marie-Tooth disease type 4B2 (CMT4B2)
  • Charcot-Marie-Tooth disease type 4B3 (CMT4B3)
  • Charcot-Marie-Tooth disease type 4C (CMT4C)
  • Charcot-Marie-Tooth disease type 4D (CMT4D)
  • Charcot-Marie-Tooth disease type 4F (CMT4F)
  • Charcot-Marie-Tooth disease type 4H (CMT4H)
  • Charcot-Marie-Tooth disease type 4J (CMT4J)
  • Charcot-Marie-Tooth disease type 4K (CMT4K)
  • Charcot-Marie-Tooth disease type 5 (CMTX5)
  • Charcot-Marie-Tooth disease type 6 (CMTX6)
  • Charcot-Marie-Tooth disease type 6B (CMT6B), hereditary motor and sensory neuropathy type VIB (HMSN6B)
  • Charcot-Marie-Tooth disease type C (CMTDIC)
  • Charcot-Marie-Tooth disease type C (CMTRIC)
  • Charcot-Marie-Tooth disease type E (CMT-DIE)
  • Charcot-Marie-Tooth disease type F (CMTDIF)
  • Charcot-Marie-Tooth disease, type 2R (CMT2R)
  • Charcot-Marie-Tooth disease, type 2W (CMT2W)
  • DRP2-associated Charcot-Marie-Tooth disease

  • Hereditary Motor Neuropathies (HMN) Subtypes
  • 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)
  • polyarticular arthritis and spinal muscular atrophy, spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME), Jankovic Rivera syndrome
  • 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)
  • Hereditary Sensory and Autonomic Neuropathy (HSAN) Subtypes
  • congenital insensitivity to pain with anhidrosis (CIPA), hereditary sensory and autonomic neuropathy type 4 (HSAN4)
  • familial dysautonomia (FD), hereditary sensory and autonomic neuropathy type 3 (HSAN3)
  • hereditary sensory and autonomic neuropathy type 1A (HSAN1A)
  • hereditary sensory and autonomic neuropathy type 1C (HSAN1C)
  • hereditary sensory and autonomic neuropathy type 2A (HSAN2A)
  • hereditary sensory and autonomic neuropathy type 2B (HSAN2B)
  • hereditary sensory and autonomic neuropathy type 2D (HSAN2D), paroxysmal extreme pain disorder (PEXPD), primary erythromelalgia, small fiber neuropathy
  • hereditary sensory and autonomic neuropathy type 5 (HSAN5)
  • hereditary sensory and autonomic neuropathy type 6 (HSAN6)
  • hereditary sensory and autonomic neuropathy type 7 (HSAN7), familial episodic pain syndrome type 3 (FEPS3)
  • hereditary sensory and autonomic neuropathy type 8 (HSAN8)
  • Hereditary Sensory Neuropathy (HSN) Subtypes
  • hereditary sensory neuropathy type 1D (HSN1D)
  • hereditary sensory neuropathy type 1E (HSN1E)
  • hereditary sensory neuropathy type 1F (HSN1F)
  • hereditary sensory neuropathy type 2C (HSN2C)
  • Riboflavin Transporter Deficiency
  • riboflavin transporter deficiency neuronopathy, Brown-Vialetto-Van Laere syndrome 1 (BVVLS1)
  • riboflavin transporter deficiency neuronopathy, Brown-Vialetto-Van Laere syndrome 2 (BVVLS2)
  • Neuropathic Amyloidosis
  • amyloidosis, Finnish type
  • hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis)
  • APOA1-related systemic amyloidosis
  • Other Disorders
  • acute intermittent porphyria (AIP)
  • agenesis of the corpus callosum with peripheral neuropathy (ACCPN), Andermann syndrome
  • Alpers-Huttenlocher syndrome (AHS), ataxia neuropathy spectrum (ANS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), progressive external ophthalmoplegia (arPEO), progressive external ophthalmoplegia with mitochondrial DNA deletions (adPEO)
  • cerebrotendinous xanthomatosis (CTX)
  • Fabry disease
  • giant axonal neuropathy 1 (GAN1)
  • hereditary motor and sensory neuropathy, Okinawa type (HMSNO)
  • hereditary neuralgic amyotrophy
  • hereditary neuropathy with or without age-related macular degeneration (HNARMD)
  • hereditary spastic paraplegia type 5A (SPG5A)
  • neuromyotonia and axonal neuropathy (NMAN)
  • peripheral neuropathy, with or without impaired intellectual development (PNRIID)
  • POLG2-related syndromic sensory neuropathy, progressive external ophthalmoplegia with mitochondrial deletions 4 (PEOA4)
  • pontocerebellar hypoplasia type 1D (PCH1D)
  • Tay-Sachs disease, beta-hexosaminidase A (HEXA) deficiency

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

Neuropathies 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
AARS NM_001605.2
AIFM1 NM_004208.3
APOA1 NM_000039.2
ARHGEF10 NM_014629.3
ASAH1 NM_177924.3
ATL1 NM_015915.4
ATL3 NM_015459.4
ATP1A1* NM_000701.7
ATP7A NM_000052.6
BAG3 NM_004281.3
BICD2 NM_001003800.1
BSCL2 NM_032667.6
CCT5 NM_012073.4
CHCHD10 NM_213720.2
COX6A1 NM_004373.3
CYP27A1 NM_000784.3
CYP7B1 NM_004820.3
DCTN1 NM_004082.4
DHTKD1 NM_018706.6
DNAJB2 NM_001039550.1
DNM2 NM_001005360.2
DNMT1 NM_001130823.1
DRP2 NM_001939.2
DST NM_001723.5; NM_015548.4
DYNC1H1 NM_001376.4
EGR2 NM_000399.3
ELP1 NM_003640.3
EXOSC9 NM_001034194.1
FBLN5 NM_006329.3
FBXO38 NM_030793.4
FGD4 NM_139241.3
FIG4 NM_014845.5
GAN NM_022041.3
GARS NM_002047.2
GDAP1 NM_018972.2
GJB1 NM_000166.5
GLA* NM_000169.2
GNB4 NM_021629.3
GSN NM_000177.4
HARS NM_002109.5
HEXA NM_000520.4
HINT1 NM_005340.6
HMBS NM_000190.3
HSPB1 NM_001540.3
HSPB3 NM_006308.2
HSPB8 NM_014365.2
IGHMBP2 NM_002180.2
INF2 NM_022489.3
KIF1A NM_004321.6
KIF5A NM_004984.2
LAS1L NM_031206.4
LITAF NM_004862.3
LMNA NM_170707.3
LRSAM1 NM_138361.5
MARS NM_004990.3
MCM3AP NM_003906.4
MED25 NM_030973.3
MFN2 NM_014874.3
MICAL1 NM_001286613.1
MME* NM_007289.2
MORC2 NM_001303256.2
MPZ NM_000530.6
MTMR2 NM_016156.5
NDRG1 NM_006096.3
NEFH NM_021076.3
NEFL NM_006158.4
NGF NM_002506.2
NTRK1 NM_001012331.1
PDK3 NM_001142386.2
PLEKHG5 NM_020631.4
PMP2 NM_002677.3
PMP22 NM_000304.3
POLG NM_002693.2
POLG2 NM_007215.3
PRDM12 NM_021619.2
PRPS1 NM_002764.3
PRX NM_181882.2
RAB7A NM_004637.5
REEP1 NM_022912.2
RETREG1 NM_001034850.2
SBF1 NM_002972.3
SBF2 NM_030962.3
SCN10A NM_006514.3
SCN11A* NM_014139.2
SCN9A NM_002977.3
SEPT9 NM_006640.4
SGPL1 NM_003901.3
SH3TC2 NM_024577.3
SIGMAR1 NM_005866.3
SLC12A6 NM_133647.1
SLC25A21 NM_030631.3
SLC25A46 NM_138773.2
SLC52A1 NM_017986.3
SLC52A2 NM_024531.4
SLC52A3 NM_033409.3
SLC5A7 NM_021815.2
SMN1, SMN2* NM_000344.3; NM_017411.3
SPG11 NM_025137.3
SPTLC1 NM_006415.3
SPTLC2 NM_004863.3
SURF1 NM_003172.3
TFG NM_006070.5
TRIM2 NM_001130067.1
TRPV4 NM_021625.4
TTR NM_000371.3
UBA1 NM_003334.3
VAPB NM_004738.4
VRK1 NM_003384.2
WNK1 NM_213655.4
YARS NM_003680.3

ATP1A1: Deletion/duplication analysis is not offered for exon 1.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MME: Deletion/duplication analysis is not offered for exons 5-6.
SCN11A: Sequencing analysis for exons 1 includes only cds +/- 10 bp.
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.