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Myofibrillar Myopathy via the FLNC 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
11337 FLNC 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11337FLNC81479 81479,81479 $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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Myofibrillar myopathy (MFM) refers to a genetically heterogeneous group of disorders sharing a homogeneous morphological pattern and, most often, onset of clinical symptoms in adulthood. Stained with trichome, abnormal muscle fibers are seen containing hyaline structures and vacuoles that contain membrane fragments from disintegrated sarcomeric Z disc and myofibrils (Selcen et al. Brain 127:439-451, 2004). With electron microscopy, affected muscle fibers reveal progressive degeneration of myofibrils beginning at the Z-disk. Immunohistochemical staining of the structurally abnormal fibers reveals abnormal expression and accumulation of several proteins, including myotilin, desmin, alpha-B crystalline, dystrophin, and β-amyloid precursor protein (Selcen et al. 2004). Clinically, patients present in adulthood with proximal and distal weakness and in some cases with cardiomyopathy. Cardiac involvement has been reported in FLNC-related MFM (Luan et al. Neuromuscul Disord 20:390-396, 2010).

Genetics

Filamin-related myofibrillar myopathy (OMIM 609524) is inherited as an autosomal dominant disorder. Filamin-C, a member of a small family of proteins known to bind actin, interacts with gamma and delta sarcoglycans (Thompson et al. J Cell Biol 148:115-126, 2000). Elevated levels of membrane-associated filamin-C have been found in patients with limb girdle muscular dystrophy type 2C (gamma sarcoglycanopathy) and dystrophinopathy (Thompson et al. 2000). A small number of pathogenic gene variants have been reported in the FLNC gene; they include missense, nonsense, small deletions and an insertion/deletion variant. A dominant-negative effect has been documented for a single nucleotide deletion within the dimerization domain of the filamin-C protein (Kono et al. Neurol 75:547-554, 2010). Other genes involved with MFM include MYOT, DES, LDB3, CRYAB, and BAG3.

Clinical Sensitivity - Sequencing with CNV PGxome

Myofibrillar myopathy due to FLNCvariants is a rare disorder. Among a cohort of 80 MFM patients diagnosed at the Mayo Clinic, only 46% were found to have variants in one of the six known causative genes (Selcen and Engel, 2010). The relative frequencies of variants found in the Mayo Clinic cohort was LDB3 (14%), MYOT (13%), DES (8%), FLNC (4%), BAG3 (4%), and CRYAB (3%). Thus, myofibrillar myopathy appears to be a genetically heterogeneous disorder, and the clinical sensitivity for testing any of the known myofibrillar myopathy-related genes is likely low.

Testing Strategy

This test provides full coverage of all coding exons of the FLNC 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

Patients with clinical features consistent with myofibrillar myopathy, demonstrated autosomal dominant inheritance, and a muscle biopsy with characteristic immunohistochemical and ultrastructural features.

Gene

Official Gene Symbol OMIM ID
FLNC 102565
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Myofibrillar Myopathy, Filamin C-Related AD 609524

Citations

  • Duygu Selcen, Andrew G Engel (2010).
  • Kono, S., et.al. (2010). PubMed ID: 20697107
  • Luan, X., et.al. (2010). PubMed ID: 20417099
  • Selcen D, Ohno K, Engel AG. 2004. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 127(Pt 2): 439-451. PubMed ID: 14711882
  • Thompson, T. G., et.al. (2000). PubMed ID: 10629222

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

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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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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.
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