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Myopathy, Congenital via the TPM3 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
TPM3 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8785TPM381479 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.


Genetic Counselors


  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Congenital fiber type disproportion (CFTD) is a genetically and clinically heterogeneous congenital myopathy usually presenting as hypotonia and delayed motor milestones before one year of age. Clinical findings among CFTD patients with TPM3 variants include proximal limb girdle weakness, weakness of neck flexion and ankle dorsiflexion, facial weakness, ptosis, and absent or decreased deep tendon reflexes (Clarke et al. Ann Neurol 63:329-337, 2008; Lawlor et al. Hum Mutat 31:176-183, 2010). Dependence on nocturnal ventilation support was a common finding in these two studies and, except for the most severely affected individual, patients remained ambulatory. Age of onset and severity is noted to vary even within the same family (Clarke et al. 2008); however, patients diagnosed as adults through family studies were aware of symptoms of weakness or myalgia as children (Lawlor et al. 2010). Histologically, type 1 muscle fibers from patients were smaller that type 2 fibers by 50% to 77% in one study (Clarke et al. 2008) and 47% in another (Lawlor et al. 2010). Marked fiber size disproportion was due to hypotrophy of type 1 fibers and hypertrophy of type 2 fibers. Typical of CFTD, overall type 1 fiber predominance, absence of type 2B fibers, and absence of other histopathology was commonly observed in patient biopsies (Clarke et al. 2008). Nemaline myopathy (NEM) is a genetically and clinically heterogeneous disorder characterized by muscle weakness, hypotonia, and the presence of rod-like structures called 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 also characterized by type 1 fiber predominance; however, the presence of nemaline bodies is a finding unique to NEM (Ryan et al. Neurol 60:665-673, 2003).


Variants in the gene encoding the muscle form of tropomyosin 3 (TPM3; OMIM 191030), also referred to as alpha-tropomyosin-SLOW, are a rare cause of nemaline myopathy (NEM1; OMIM 609284) and the most common cause of congenital fiber type disproportion (CFTD; OMIM 255310). Myopathy due to TPM3 variants may be inherited as an autosomal dominant or recessive disorder (Lawlor et al. 2010; Clarke et al 2008; Ryan et al. 2001). De novo TPM3 variants have also been documented to cause CFTD (Clarke et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

TPM3 variants are the most common known cause of CFTD. Clinical sensitivity should be high when type 1 fiber hypotrophy is >50% in the absence of other histopathological findings. Lawlor et al. (2009) found six of 13 patients with a diagnosis of CFTD based on type 1 fiber hypotrophy to have variants in this gene. In another cohort of 23 CFTD families, six were found to have TPM3 variants (Clarke et al. 2008). It is estimated that TPM3 variants account for <3% of NEM cases (Wattanasirichaigoon et al. Neurol 59:613-617, 2002).

Testing Strategy

This test provides full coverage of all coding exons of the TPM3 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 NEM and muscle biopsy studies showing nemaline bodies and individuals with clinical symptoms consistent with CFTD with muscle biopsies demonstrating fiber type disproportion in the absence of nemaline bodies and other histological findings suggestive of another diagnosis. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TPM3.


Official Gene Symbol OMIM ID
TPM3 191030
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Congenital Fiber Type Disproportion AR, AD 255310
Nemaline Myopathy 1 AR, AD 609284

Related Tests

α-Actin (Skeletal Muscle Form)-Related Myopathy via the ACTA1 Gene
Comprehensive Cardiology Panel


  • Clarke NF, Kolski H, Dye DE, Lim E, Smith RLL, Patel R, Fahey MC, Bellance R, Romero NB, Johnson ES, Labarre-Vila A, Monnier N, et al. 2008. Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann. Neurol. 63: 329–337. PubMed ID: 18300303
  • Lawlor MW, Dechene ET, Roumm E, Geggel AS, Moghadaszadeh B, Beggs AH. 2010. Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. Hum. Mutat. 31: 176–183. PubMed ID: 19953533
  • 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
  • Wattanasirichaigoon, D., et.al. (2002). "Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy." Neurology 59(4): 613-7. PubMed ID: 12196661


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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