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Type VI Collagenopathy via the COL6A1 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
11197 COL6A1 81407 81407,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11197COL6A181407 81407,81479 $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

Ullrich congenital muscular dystrophy (UCMD; OMIM 254090) and Bethlem myopathy (OMIM 158810) represent the spectrum of clinical disorders with abnormal type 6 collagen. Bethlem myopathy is characterized by proximal weakness and variable contractures. Most often affected by contractures are elbows, ankles, and fingers. The earliest presenting signs are decreased fetal movement, neonatal hypotonia, and congenital contractures (Jobsis et al. Brain 122:649-655, 1999). Delayed motor milestones, muscle weakness, and contractures are evident in cases of Bethlem myopathy with early childhood onset (Lampe et al. GeneReviews, 2007). The clinical course in adult-onset patients is typically slow but relentless; approximately two-thirds of patients over age 50 require ambulatory support (Jobsis et al., 1999). UCMD is characterized by congenital muscle weakness, proximal joint contractures, and striking hyperlaxity of distal joints (Lampe and Bushby. J Med Genet 42:673-685, 2005). Affected children rarely gain the ability to walk independently and spinal rigidity and scoliosis develop. Respiratory failure in the first and second decade of life is a common cause of death (Lampe and Bushby, 2005). Serum CK levels are normal or mildly elevated in both Bethlem myopathy and UCMD; however, muscle biopsies from UCMD patients are more likely to be dystrophic and show absent or reduced immunostaining of collagen VI (Higuchi et al. Neuromuscul Disord. 13:310-316, 2003). Intelligence is normal in Bethlem myopathy and UCMD patients.

Genetics

Most cases of Bethlem myopathy reported to date have demonstrated autosomal dominant inheritance of COL6A1, COL6A2, or COL6A3 variants (Lampe and Bushby, 2005; Jobsis et al., 1999). Once thought to be strictly a recessive condition, UCMD has been shown to be inherited in a dominant manner in numerous cases (e.g., Pan et al. Am J Hum Genet 73:355-369, 2003). A dominant-negative effect underlies pathogenicity of dominantly inherited UCMD (Pan et al., 2003; Baker et al., Hum Mol Genet 14:279-293, 2005), while most cases of recessive UCMD result from truncating variants. Substitutions affecting the conserved Gly-X-Y motif of all three COL6 genes and splice site variants affecting exon 14 of COL6A1 are common pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Sequence analysis using genomic DNA from peripheral blood was found to have clinical sensitivity of 66%, 56%, and 79% among patients classified as having typical Bethlem Myopathy, severe Bethlem Myopathy, and Ulrich Congenital Muscular Dystrophy, respectively (Lampe et al. J Med Genet 42:108-120, 2005).

Testing Strategy

This test provides full coverage of all coding exons of the COL6A1 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 and pathological features consistent with Bethlem myopathy or UCMD. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in COL6A1.

Gene

Official Gene Symbol OMIM ID
COL6A1 120220
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Bethlem Myopathy AR, AD 158810
Ullrich Congenital Muscular Dystrophy AR, AD 254090

Citations

  • Baker NL, Mörgelin M, Peat R, Goemans N, North KN, Bateman JF, Lamandé SR. 2005. Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy. Human Molecular Genetics 14: 279–293. PubMed ID: 15563506
  • Jöbsis GJ, Boers JM, Barth PG, Visser M De. 1999. Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures. Brain 122: 649–655. PubMed ID: 10219778
  • Lampe AK, Bushby KM. 2005. Collagen VI related muscle disorders. Journal of Medical Genetics 42: 673–685. PubMed ID: 16141002
  • Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, Marie SK, Chu ML, Swoboda K, Muntoni F, Bonnemann CG, Flanigan KM, Bushby KM, Weiss RB. 2005. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet 42: 108-120. PubMed ID: 15689448
  • Lampe AK, Flanigan KM, Bushby KM, Hicks D. 2012. Collagen Type VI-Related Disorders. 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: 20301676
  • Nishiguchi, K. M., et.al. (2005). "Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases." Hum Mutat 25(3): 248-58. PubMed ID: 15712225
  • Pan T-C, Zhang R-Z, Sudano DG, Marie SK, Bonnemann CG, Chu M-L. 2003. New Molecular Mechanism for Ullrich Congenital Muscular Dystrophy: A Heterozygous In-Frame Deletion in the COL6A1 Gene Causes a Severe Phenotype. Am J Hum Genet 73: 355–369. PubMed ID: 12840783

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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