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Nemaline Myopathy (NEM2) via the Nebulin (NEB) Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
NEB 81408 81408,81479 $1590
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
1772NEB81408 81408,81479 $1590 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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

Mutations in the nebulin gene (NEB) are the most common cause of autosomal recessive nemaline myopathy (NEM). NEM is a genetically and clinically heterogeneous disorder characterized by muscle weakness, hypotonia and the presence of nemaline bodies in skeletal muscle fibers. Muscle weakness is typically observed in affected neonates or infants, although later onset cases are reported (Ryan et al. 2001). The most severely affected muscle groups are proximal limb, facial, bulbar, and respiratory muscles. Deep tendon reflexes are absent or depressed. Histologically, NEM is characterized by type 1 fiber predominance and the presence of rod-like structures called nemaline bodies upon Gomori trichrome staining of skeletal muscle (Ryan et al. 2003). Six clinical types of NEM have been delineated based on age of onset, severity and distribution of weakness, and respiratory function (Ryan et al. 2001; North and Ryan 2002). Nebulin gene mutations more often cause typical neonatal onset disease, although NEB mutations have been found in every clinical form of NEM (Lehtokari et al. 2006). Overlap among the six clinical groups is significant, and adults are sometimes diagnosed only after another family member has presented with typical signs.


To date, mutations in six genes have been shown to cause nemaline myopathy. Mutations in ACTA1 (NEM3) and NEB (NEM2) are the only relatively common causes, accounting for 15-25% and up to 50%, respectively, of all studied cases (Ryan et al. 2001; North and Ryan. 2002). All reported cases of NEB-associated NEM demonstrate autosomal recessive inheritance (Lehtokari et al. 2006; Lehtokari et al. 2014). In the largest cohort published to date, Lehtokari et al. (2014) identified 212 NEB mutations segregating with autosomal recessive NEM in 159 families. In this study, pathogenic mutations are found in most exons of the NEB gene, including the triplicate region (exons 82-105). The majority of these mutations (Lehtokari et al. 2014) were splice site variants (34%), frameshift mutations (32%), and nonsense mutations (23%). Reported pathogenic missense variants appear to be less common (~7%). The only common NEB mutation is an exon 55 deletion found at a carrier frequency of about 1% among people of Ashkenazi Jewish ancestry (Anderson et. al. 2004).

Clinical Sensitivity - Sequencing with CNV PG-Select

Up to 50% of all known nemaline myopathy cases are caused by mutations in NEB (North and Ryan 2002).

Gross deletions/duplications account for ~4% of all reported NEB mutations (Lehtokari et al. 2014). An exon 55 deletion is the only common deletion found at a carrier frequency of about 1% among people of Ashkenazi Jewish ancestry (Anderson et. al. 2004). A separate PCR based assay for this common deletion is available (#356).

Testing Strategy

This test provides full coverage of all coding exons of the NEB gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Exons 82-105 of the NEB gene are organized in three highly homologous blocks of 8 exons each making this region difficult to analyze by NextGen Sequencing. Due to the homology, there are mapping and alignment issues which may cause variants in this region to go undetected. We employ a novel long-range 2-step PCR with Sanger sequencing to analyze this region of the NEB gene which allows correct exon and zygosity assignment.

Indications for Test

Individuals with symptoms consistent with the typical congenital form of nemaline myopathy. Individuals whose muscle biopsies show predominance of type 1 fibers and nemaline bodies. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NEB.


Official Gene Symbol OMIM ID
NEB 161650
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Nemaline Myopathy 2 AR 256030

Related Tests

Nemaline Myopathy Panel
Nemaline Myopathy via the NEB Exon 55 Deletion
Nemaline Myopathy via the NEB Gene, Exons 82-105 (Triplicate Repeat Region)


  • Anderson SL, Ekstein J, Donnelly MC, Keefe EM, Toto NR, LeVoci LA, Rubin BY. 2004. Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene. Hum Genet 115: 185-190. PubMed ID: 15221447
  • Lehtokari V-L, Kiiski K, Sandaradura SA, Laporte J, Repo P, Frey JA, Donner K, Marttila M, Saunders C, Barth PG, Dunnen JT den, Beggs A, Clarke NF, North KN, Laing NG, Romero NB, Winder TL, Pelin K, Wallgren-Pettersson C. 2014. Mutation Update: The Spectra of Nebulin Variants and Associated Myopathies. Hum. Mutat. 35:1418-1426 PubMed ID: 25205138
  • Lehtokari VL, Pelin K, Sandbacka M, Ranta S, Donner K, Muntoni F, Sewry C, Angelini C, Bushby K, Van den Bergh P, Iannaccone S, Laing NG, Wallgren-Pettersson C. 2006. Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Hum Mutat 27: 946-956. PubMed ID: 16917880
  • North KN, Ryan MM. 2002. Nemaline Myopathy. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301465
  • Ryan MM, Ilkovski B, Strickland CD, Schnell C, Sanoudou D, Midgett C, Houston R, Muirhead D, Dennett X, Shield LK, Girolami U De, Iannaccone ST, Laing NG, North KN, Beggs AH. 2003. Clinical course correlates poorly with muscle pathology in nemaline myopathy. Neurology 60: 665673. PubMed ID: 12601110
  • Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, Laing NG, Beggs AH, North KN. 2001. Nemaline myopathy: a clinical study of 143 cases. Ann. Neurol. 50: 312320. PubMed ID: 11558787


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

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