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Charcot-Marie-Tooth Type 2E/1F via the NEFL Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
NEFL 81405 81405,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8413NEFL81405 81405,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Charcot Marie Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN) is a large group of inherited disorders of the peripheral nerves. The progressive degeneration of motor nerves results in weakness and atrophy of the distal muscles; and the degeneration of sensory nerves leads to decreased sensation, tingling and numbness in the legs, feet, arms and hands and neuropathic pain. The age of onset varies from childhood to mid adulthood. Symptoms usually begin with weakness and atrophy in the muscle of the legs and feet. As the disease progresses, weakness and atrophy of the muscles of the arms and hands may occur. CMT is heterogeneous in regards to symptoms, severity and progression rate. Although the disease may lead to disability and respiratory difficulty, life expectancy is usually unaffected. Most common symptoms include foot deformity, loss of balance, hammertoes, foot drop, frequent tripping and falls, and reduced manual dexterity. Diagnosis is based on clinical features, family history, neurological examination, and electromyography (EMG) and nerve conduction velocity (NCV) findings (Pareyson and Marchesi 2009; Bird 2015). CMT affects approximately 1 in 3,300 people.

Pathogenic variants in the NEFL gene can result in CMT neuropathies with variable clinical and electrophysiological expression. Many patients have been reported with an early disease onset and are usually more severely affected (Jordanova 2003; Sivera et al. 2013).


Charcot-Marie-Tooth type 2E/1F is inherited in both an autosomal dominant and autosomal recessive manner due to pathogenic variants in NEFL, located on chromosome 8p21. The NEFL gene encodes the neurofilament light chain polypeptide (NEFL) which is one of the most abundant cytoskeletal components of the neuron. Genetic defects of NEFL found to date include missense, nonsense, and small deletions/insertions (Human Gene Mutation Database). In one study, a genotype/phenotype correlation of NEFL pathogenic variants could not be identified. However, the authors suggested that pathogenic variants in the NEFL protein head domain can cause more severe motor and sensory NCV slowing than pathogenic variants in the coil 2B domain (Miltenberger-Miltenyi et al. 2007). Autosomal dominant inheritance is most commonly reported; however, a few recessive cases have been reported (Yum et al. 2009, Abe et al. 2009). The recessive cases do not always exhibit a more severe phenotype (Abe et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

A genetic etiology can be identified in approximately 50-70% of individuals with CMT (Saporta et al. 2011; Rossor et al. 2013). Specifically, a molecular diagnosis can be identified in approximately 80-85% of individuals with demyelinating neuropathy (CMT1). CMT2E/1F (<5% of all CMT1) is associated with pathogenic variants in NEFL (Bird 2015). In one study of 323 patients with different CMT phenotypes, 2% of cases were found to have a pathogenic NEFL variant (Jordanova 2003).

Thus far, no large deletions or duplications involving the NEFL gene have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the NEFL gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with clinical symptoms consistent with Charcot-Marie-Tooth. Testing is also indicated for family members of patients who have known NEFL pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NEFL.


Official Gene Symbol OMIM ID
NEFL 162280
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Abe A. et al. 2009. Journal of Human Genetics. 54: 94-7. PubMed ID: 19158810
  • Bird and Bird. 2015. PubMed ID: 20301532
  • Bird T.D. 2015. Charcot-Marie-Tooth Neuropathy Type 1. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301384
  • Human Gene Mutation Database (Bio-base).
  • Jordanova A. 2003. Brain. 126: 590-597. PubMed ID: 12566280
  • Miltenberger-Miltenyi G. et al. 2007. Archives of Neurology. 64: 966-70. PubMed ID: 17620486
  • Pareyson D., Marchesi C. 2009. The Lancet Neurology. 8: 654–67. PubMed ID: 19539237
  • Rossor A.M. et al. 2013. Nature Reviews Neurology. 9: 562-571. PubMed ID: 24018473
  • Saporta et al. 2011. PubMed ID: 21280073
  • Sivera R. et al. 2013. Neurology. 81: 1617–1625. PubMed ID: 24078732
  • Yum S.W. et al. 2009. Annals of Neurology. 66: 759-70. PubMed ID: 20039262


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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