Nemaline Myopathy 5 (Amish Nemaline Myopathy) via the TNNT1 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
11755 TNNT1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11755TNNT181479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Variants in the troponin T1 gene (TNNT1; OMIM 191041) are one cause of autosomal recessive nemaline myopathy (NEM5; OMIM 605355). 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. Neurol 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). Troponin T1-associated NEM is a lethal form of nemaline myopathy described only in the Old Order Amish community of Pennsylvania (Johnston et al. Am J Hum Genet 67:814-821, 2000). Newborns affected with TNNT1-associated nemaline myopathy are hypotonic and have shoulder and hip contractures along with tremors. Contractures and muscle weakness progressively worsen and patients develop pectus carinatum before life-threatening respiratory symptoms develop in the second year of life (Johnston et al. 2000).

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). Among Old Order Amish of Lancaster County, Pennsylvania, a p.Glu180* founder variant in exon 11 of the TNNT1 gene was found to account for the autosomal recessive nemaline myopathy in this community (Johnston et al. 2000; Jin et al. J Biol Chem 278:26159-26165, 2003). The incidence of NEM5 among this population is ~1/500 (Johnston et al. 2000).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical and analytical sensitivity for testing symptomatic individuals of the Old Order Amish is expected to be high. Clinical sensitivity among other populations is not known.

Testing Strategy

This test provides full coverage of all coding exons of the TNNT1 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals, particularly of the Old Order Amish, with symptoms consistent with the lethal form of nemaline myopathy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TNNT1.

Gene

Official Gene Symbol OMIM ID
TNNT1 191041
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nemaline Myopathy 5 AR 605355

Citations

  • Johnston JJ, Kelley RI, Crawford TO, Morton DH, Agarwala R, Koch T, Schäffer AA, Francomano CA, Biesecker LG. 2000. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet 67: 814-821. PubMed ID: 10952871
  • North, Kathryn, Ryan, Monique M (2009). "Nemaline Myopathy."
  • 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

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.

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

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ORDER OPTIONS

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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.

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