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Myotilinopathy via the MYOT 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
MYOT 81405 81405,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8579MYOT81405 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

Variants in the myotilin gene (MYOT), also referred to as the titin immunoglobulin domain protein gene (TTID), cause limb girdle muscular dystrophy type 1A (LGMD1A; OMIM 159000; Hauser et al. Hum Mol Genet 9:2141-2147, 2000) and myofibrillar myopathy (OMIM 609200; Selcen and Engel. Neurology 62:1363-1371, 2004). Patients with the LGMD phenotype exhibit distal weakness with mean age at onset of 27 years. Proximal weakness develops later in life, and approximately half of all patients exhibit a distinct nasal, dysarthric pattern of speech (Hauser at al. Amer J Hum Genet 71:1428-1432, 2002). CK levels are generally elevated 1.6 to 9-fold above normal range (Hauser et al. 2002). Myotilin-related MFM exhibits later onset (50 - 77 years) and has features of peripheral neuropathy with hyporeflexia, cardiomyopathy, and distal weakness greater than proximal weakness (Selcen and Engel, 2004). 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). Based upon studies of small cohorts, LGMD1A patients developed hyporeflexia later in the disease than myotilin-related MFM patients, thus tentatively differentiating these allelic disorders.


Myotilinopathy is inherited in an autosomal dominant manner. The MYOT gene (OMIM 604103) encodes myotilin, a sarcomeric protein that binds actin either alone or in conjunction with alpha-actinin, an actin crosslinking protein. Thus, myotilin plays a key role in stabilization and anchorage of thin filaments, which may be a prerequisite for correct Z disc organization (Salmikangas et al. Hum Mol Genet 12:189-203, 2003). Nearly all reported MYOT variants result in amino acid substitutions in the serine rich exon 2. One missense variant in exon 9 has been reported to be causative for LGMD1A (Shalby et al. J Neuropath Exp Neurol 68:701-707, 2009). Other genes involved with MFM include DES, FLNC, LDB3, CRYAB, and BAG3.

Clinical Sensitivity - Sequencing with CNV PGxome

Myotilinopathy is a rare disorder (see for example, Moore et al. J Neuropathol Exp Neurol. 65:995-1003, 2006). Hauser et al. screened 86 muscular dystrophy families, 44 of which demonstrated autosomal dominant inheritance. One with a causative MYOT variant was found (Hauser et al. Am J Hum Genet 71:1428–1432, 2002). The relative frequencies of variants found in the Mayo Clinic MFM cohort was LDB3 (14%), MYOT (13%), DES (8%), FLNC (4%), BAG3 (4%), and CRYAB (3%) (Selcen and Engel, GeneReviews 2010).

Testing Strategy

This test provides full coverage of all coding exons of the MYOT 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 LGMD or myofibrillar myopathy and autosomal dominant inheritance. Symptomatic individuals with muscle biopsies demonstrating centrally-located nuclei and fiber size variation.


Official Gene Symbol OMIM ID
MYOT 604103
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Limb-Girdle Muscular Dystrophy, Type 1A AD 159000
Myotilinopathy AD 609200


  • Duygu Selcen, Andrew G Engel (2010). "Myofibrillar Myopathy."
  • Hauser, M. A., et.al. (2000). "Myotilin is mutated in limb girdle muscular dystrophy 1A." Hum Mol Genet 9(14): 2141-7. PubMed ID: 10958653
  • Hauser, M. A., et.al. (2002). "myotilin Mutation found in second pedigree with LGMD1A." Am J Hum Genet 71(6): 1428-32. PubMed ID: 12428213
  • Moore A. 2006. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. Journal of Medical Genetics 43: 326-333. PubMed ID: 16055928
  • Salmikangas, P., et.al. (2003). "Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly." Hum Mol Genet 12(2): 189-203. PubMed ID: 12499399
  • 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
  • Selcen, D., Engel, A. G. (2004). "Mutations in myotilin cause myofibrillar myopathy." Neurology 62(8): 1363-71. PubMed ID: 15111675
  • Shalaby, S., et.al. (2009). "Defective myotilin homodimerization caused by a novel mutation in MYOT exon 9 in the first Japanese limb girdle muscular dystrophy 1A patient." J Neuropathol Exp Neurol 68(6): 701-7. PubMed ID: 19458539


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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