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.
Genes tested
Primary panel
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
ARHGEF10 CCT5 HSPB3 LAS1L MICAL1 SCN10A SGPL1 SLC25A21 SLC52A1
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.
Order test
Primary panel (102 genes)
Customized gene selection (0 included, 0 excluded)
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)
Customized gene selection (0 included, 0 excluded)
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
Clinical information
Disorders tested
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
Clinical description
To view the complete clinical description of this panel, click here.
Inheritance
Neuropathies can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.
Assay
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. In addition, the analysis covers the select non-coding variants specifically defined in the table below. 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 3, 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.
