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Nemaline Myopathy 7 via the CFL2 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
9023 CFL2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9023CFL281479 81479,81479 $890 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 backbone).

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

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Variants in the cofilin-2 gene (CFL2; OMIM 601443) are one cause of autosomal recessive nemaline myopathy (NEM7; OMIM 610687). 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. Ann Neurol 50:312-320, 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. Neurology 60:665-673, 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. GeneReviews, 2009). CFL2-associated nemaline myopathy is apparently a rare disorder. Two siblings among a large cohort of unrelated NEM patients were found to have a homozygous CFL2 missense variant (Agrawal et al. Am J Hum Genet 80:162-167, 2007). The clinical presentation in the two affected sibs was like that of typical NEM, except facial muscles appeared to be spared and foot drop was not noted. Hypotonia was present at birth, and early motor milestones were delayed. Both patients attained the ability to walk at least short distances but could not run and experienced frequent falls. Muscle biopsies from the patients showed nemaline rods, minicores, type 1 fiber predominance, and marked fiber size variability.

Genetics

To date, variants in six genes have been shown to cause nemaline myopathy. Variants in ACTA1 (NEM3) and NEB (NEM2) are the only relatively common causes (Ryan et al. 2001). Cofilin-2, a skeletal muscle protein involved with alpha actin assembly, has been found to be mutated in one family (Argawal et al. 2007). NEM7 is inherited as an autosomal recessive disorder secondary to CFL2 variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Cofilin-2 associated nemaline myopathy is probably a rare disorder. Argawal et al. (2007) found two sibs with CFL2 gene variants among a cohort of 113 unrelated patients with nemaline myopathy and 58 patients with other forms of congenital myopathy. Another report found no CFL2 variants among a cohort of 50 patients (Thirion et al. Eur J Biochem 268:3473-3482, 2001).

Testing Strategy

This test provides full coverage of all coding exons of the CFL2 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 symptoms consistent with the nemaline myopathy and negative studies for the more common causes of this disorder. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CFL2.

Gene

Official Gene Symbol OMIM ID
CFL2 601443
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nemaline Myopathy 7 AR 610687

Related Test

Name
Nemaline Myopathy Panel

Citations

  • Agrawal, P. B., et.al. (2007). PubMed ID: 17160903
  • North, Kathryn, Ryan, Monique M (2009).
  • 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: 665–673. 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: 312–320. PubMed ID: 11558787
  • Thirion, C., et.al. (2001). PubMed ID: 11422377

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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