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Limb Girdle Muscular Dystrophy Type 1F via the TNPO3 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
11759 TNPO3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11759TNPO381479 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

Limb girdle muscular dystrophy (LGMD) is a descriptive term for a group of disorders with atrophy and weakness of proximal girdle muscles and typical sparing of the heart and bulbar muscles. Clinical severity, age of onset, and disease progression are highly variable among the subtypes (Sáenz et al. 2005). Serum creatine kinase levels are typically elevated, and muscle biopsies demonstrate a dystrophic process. For comprehensive reviews, see Pegoraro and Hoffman (2012) and Nigro and Savarese (2014).

Limb girdle muscular dystrophy type 1F has been described in one large Spanish family of about 50 individuals (Melià et al. 2013; Torella et al. 2013). In this family, a presumed pathogenic TNPO3 variant was identified by whole genome sequencing and co-segregated with 29 affected individuals and was absent in 20 unaffected individuals. The individuals in this family presented with limb girdle and distal muscle weakness with variable distribution, severity, and rate of progression. Some individuals presented in infancy with mild delay in motor skills, whereas two of the most severe cases presented with an Emery-Dreifuss-like phenotype. Overall, the disorder typically presents in late childhood or early adolescence and less frequently in adulthood. About 40% of the cases had elevated creatine kinase levels. Muscle biopsy analysis revealed increased variability of fiber size and shape, increased endo- and peri-mysial connective tissue, occasional central nuclei, rimmed vacuoles and autophagic vacuoles.

Genetics

Limb girdle muscular dystrophy type 1F is an autosomal dominant disorder caused by defects in the TNPO3 gene (Melià et al. 2013; Torella et al. 2013). In a very large Spanish family, a small deletion in the termination codon that leads to an extended protein product was reported to segregate with all affected individuals (c.2771del, p.*924Cysfs*16). Only one additional unrelated patient with a missense variant has been reported thus far. The TNPO3 gene encodes transportin 3, a protein involved in translocation of proteins from the cytoplasm to the nucleus. It is unknown if these dominant variants cause disease due to haploinsufficiency or to a dominant-negative mechanism.

Clinical Sensitivity - Sequencing with CNV PGxome

Too few cases of LGMD1F have been reported to provide a numeric estimate of clinical or analytical sensitivity. However, pathogenic variants in TNPO3 appear to be a rare cause of LGMD. Analytical sensitivity could be high as the reported pathogenic variants are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the TNPO3 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 a limb-girdle distribution of weakness.

Gene

Official Gene Symbol OMIM ID
TNPO3 610032
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Limb-Girdle Muscular Dystrophy, Type 1F AD 608423

Citations

  • Melià M.J. et al. 2013. Brain : a Journal of Neurology. 136: 1508-17. PubMed ID: 23543484
  • Nigro V., Savarese M. 2014. Acta Myologica. 33: 1-12. PubMed ID: 24843229
  • Pegoraro E., Hoffman E.P. 2012. Limb-Girdle Muscular Dystrophy Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301582
  • Sáenz A. et al. Brain 128: 732–42. PubMed ID: 15689361
  • Torella A. et al. 2013. Plos One. 8: e63536. PubMed ID: 23667635

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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