Invitae Comprehensive Neuropathies Panel


Test description

The Invitae Comprehensive Neuropathies Panel analyzes up to 79 genes associated with hereditary neuropathies including Charcot-Marie-Tooth disease, hereditary motor neuropathies and hereditary sensory and autonomic neuropathies, as well as several other genes associated with rare neuropathies. These genes were curated based on the available evidence to date to provide a comprehensive test for these conditions.

This test is Invitae’s broadest neuropathy panel. Given the clinical overlap between different neuropathies, comprehensive testing enables a more efficient evaluation of multiple conditions using a single test. It is particularly helpful if the inheritance pattern is unclear from the individual’s family history, the individual/family has an unusual presentation or family history, or other more targeted panels have been evaluated and are negative. Individuals with clinical signs and symptoms of sensory and/or motor neuropathy may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance, help determine which relatives are at risk, or qualify affected individuals to enroll in certain clinical trials.

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Primary panel (68 genes)


INF2: Readthrough analysis is not offered for exon 8.

Add-on preliminary-evidence genes (11 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. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Hereditary neuropathies can manifest as a combination of sensory and motor neuropathy, isolated motor neuropathy or isolated sensory neuropathy (sometimes with autonomic neuropathy).

Charcot-Marie-Tooth disease
Charcot-Marie-Tooth (CMT) disease is a group of hereditary neuropathies characterized by progressive muscle weakness and sensory loss in the arms and legs. Individuals in the early stages of the disease often present with clumsiness due to numbness in the feet. As the disease progresses, the lack of nerve conduction to the extremities can also result in depressed tendon reflexes, muscle atrophy—especially at the ankles and hands, and foot deformities such as high, arched feet or hammertoes. Symptoms are caused by the impairment of the ability of peripheral nerves to conduct signals throughout the body, which results in reduced motor control and sensation in the arms and legs, especially at the ankles and wrists. Different subtypes of CMT are caused by different types of peripheral nerve abnormalities: abnormalities in the peripheral nerve axons (axonal types), abnormalities in the myelin sheath that insulates peripheral nerve axons (demyelinating types), or (rarely) both types of abnormalities (intermediate). Nerve conduction studies can be used in combination with inheritance pattern to determine the type of CMT (CMT1, 2, 4, X, or dominant intermediate), but genetic testing is needed to identify the specific subtype (e.g., CMT1A versus CMT1B).

Hereditary motor neuropathies
Hereditary motor neuropathies (HMNs), in some cases referred to as spinal muscular atrophies (SMAs), are a clinically and genetically heterogeneous group of disorders characterized by loss of motor neurons within the spinal cord, resulting in weakness and muscle wasting. The weakness and wasting is primarily distal, but in some cases can be proximal or combined proximal/distal. Typical clinical findings include slowly progressive muscle weakness and wasting. Onset of symptoms varies from the prenatal period to adulthood. Some forms of HMN also have minor involvement of the sensory neurons. Other features are variable depending on the causative gene, and may include vocal cord paralysis, facial weakness, pyramidal signs, and arthrogryposis. Many genes associated with HMN can also cause other forms of neuropathy with overlapping symptoms, such as Charcot-Marie-Tooth disease.

Hereditary sensory and autonomic neuropathies
Hereditary sensory and autonomic neuropathies (HSAN) are a clinically heterogeneous group of disorders that predominantly affect the sensory neurons of the peripheral nervous system, with or without autonomic neuron involvement. Loss of sensory neuron function can lead to complications including frequent injuries, ulcerations, bone infections and amputation. Possible autonomic features include anhidrosis, hyperhidrosis, abnormal blood pressure fluctuations, and gastrointestinal issues. Sensory abnormalities are often more significant than autonomic abnormalities. Motor neuron involvement may also occur in some individuals. Depending on the causative gene, other findings may also be present, such as hearing loss, gait impairment, decreased tendon reflexes, hypotonia, delayed development, and congenital insensitivity to pain. Age of onset varies from infancy to adulthood.

Across CMT types 1, 2, 4, X, and dominant intermediate, four genes account for the majority of cases (50%-75%): PMP22, MPZ, GJB1, and MFN2. BSCL2 is one of the most common causes of distal HMN, and accounts for 7-12% of affected individuals. The HSPB1 and HSPB8 genes each account for less than 5% of individuals with distal HMN. Pathogenic variants in the SPTLC1, NTRK1, and SPTLC2 genes account for 12%, 6% and 5% of individuals with HSAN, respectively. This panel also includes other genes that have been identified as causes of hereditary neuorpathies, although the exact contribution of these genes to the overall detection rate is not known and is dependent on the clinical presentation of the individual.

Neuropathies can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.

Hereditary neuropathies are a diverse group of disorders, and the penetrance (the chance that someone who inherits a genetic predisposition will go on to manifest the disorder) is not always known. Where known, penetrance is usually high, but is age age-dependent, and there may be variability in age of onset and symptom severity. Nonpenetrance is reported for some genes, including ATL1 and SPTLC1.

Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system. Overall prevalence of CMT is usually reported as 1 in 2,500, although several more recent epidemiological studies reported prevalences of CMT ranging from 1 in 1,214 (in Norway) to 1 in 6,500 (in the United Kingdom). It is possible these figures may be an underestimation of the prevalence of CMT due to under-diagnosis of mild or late-onset cases. Hereditary motor neuropathies are a rare group of disorders, and the overall prevalence of these conditions is unknown. The overall prevalence of HSAN is unknown, although frequencies of different forms of HSAN can very by ethnicity. Familial dysautonomia (HSAN3) is more common in the Ashkenazi Jewish population, with an estimated incidence of 1 in 3,700. The prevalence of WNK1-associated HSAN2A is increased in the French Canadian population.

Hereditary neuropathies are a heterogeneous group of disorders. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform family planning.

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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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AARS NM_001605.2
AIFM1 NM_004208.3
ATL1 NM_015915.4
ATL3 NM_015459.4
ATP7A NM_000052.6
BICD2 NM_001003800.1
BSCL2 NM_032667.6
CCT5 NM_012073.3
CHCHD10 NM_213720.2
DCTN1 NM_004082.4
DNAJB2 NM_001039550.1
DNM2 NM_001005360.2
DNMT1 NM_001130823.1
DST NM_001723.5
DYNC1H1 NM_001376.4
EGR2 NM_000399.3
FAM134B NM_001034850.2
FBXO38 NM_030793.4
FGD4 NM_139241.3
FIG4 NM_014845.5
FLRT1 NM_013280.4
GAN NM_022041.3
GARS NM_002047.2
GDAP1 NM_018972.2
GJB1 NM_000166.5
GNB4 NM_021629.3
HARS NM_002109.5
HINT1 NM_005340.6
HSPB1 NM_001540.3
HSPB3 NM_006308.2
HSPB8 NM_014365.2
IGHMBP2 NM_002180.2
IKBKAP NM_003640.3
INF2* NM_022489.3
KIF1A NM_004321.6
LAS1L NM_031206.4
LITAF NM_004862.3
LMNA NM_170707.3
LRSAM1 NM_138361.5
MARS NM_004990.3
MED25 NM_030973.3
MFN2 NM_014874.3
MORC2 NM_014941.2
MPZ NM_000530.6
MTMR2 NM_016156.5
NDRG1 NM_006096.3
NEFL NM_006158.4
NGF NM_002506.2
NTRK1 NM_001012331.1, NM_002529.3
PDK3 NM_001142386.2
PLEKHG5 NM_020631.4
PMP22 NM_000304.3
PRDM12 NM_021619.2
PRPS1 NM_002764.3
PRX NM_181882.2
RAB7A NM_004637.5
REEP1 NM_022912.2
SBF2 NM_030962.3
SCN11A NM_014139.2
SCN9A NM_002977.3
SETX NM_015046.5
SH3TC2 NM_024577.3
SIGMAR1 NM_005866.3
SLC25A46 NM_138773.2
SLC52A2 NM_024531.4
SLC52A3 NM_033409.3
SLC5A7 NM_021815.2
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
UBA1 NM_003334.3
VAPB NM_004738.4
VRK1 NM_003384.2
WNK1 NM_018979.3
YARS NM_003680.3

INF2: Readthrough analysis is not offered for exon 8.