• Test code: 03370
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Type VI Collagenopathy Panel

Test description

The Invitae Type VI Collagenopathy Panel analyzes up to four genes associated with type VI collagenopathies, which represent a variable spectrum of phenotypes, including Bethlem myopathy 1 (BTHLM1) and Ullrich congenital muscular dystrophy 1 (UCMD1), which are characterized by muscle weakness and contractures. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of type VI collagenopathies.

Given that type VI collagenopathies are a heterogeneous group of disorders, identification of the underlying genetic cause can help predict outcome and inform recurrence risk.

Order test

Primary panel (3 genes)
Add-on Gene for Type VI Collagenopathy (1 gene)

Clinicians may choose to add-on the COL12A1 gene. Pathogenic variants in the COL12A1 gene are associated with Bethlem myopathy 2 (BTHLM2) and Ullrich congenital muscular dystrophy 2 (UCMD2), conditions which share clinical features with the type VI collagenopathies. Depending on the clinical presentation of the individual and within the context of additional laboratory results, clinicians may wish to broaden analysis by including this gene, which can be added at no additional charge.


Alternative tests to consider

For a broader analysis of genes associated with myopathy, clinicians may consider the Invitae Congenital Myopathy Panel, or the Invitae Comprehensive Myopathy Panel. For a broader analysis of genes associated with muscular dystrophy, clinicians may consider either the Congenital Muscular Dystrophy Panel or the Comprehensive Muscular Dystrophy Panel. These broader panels can be ordered at no additional charge.

For a broader analysis of the genetics of hereditary neuromuscular disorders (muscular dystrophies, myopathies, and congenital myasthenic syndrome):

Type VI collagenopathies represent a variable spectrum of disorders that are characterized by muscle weakness and contractures. They range from the severe Ullrich congenital muscular dystrophy 1 (UCMD1) to the milder Bethlem myopathy 1 (BTHLM1). Intermediate disease presentations may also be observed. UCMD1 typically presents in the neonatal period with congenital muscle weakness, hypotonia, contractures, hip dislocation, and significant hyperlaxity of distal joints. Affected individuals have delayed motor development, progressive muscle weakness, and generalized muscle atrophy. BTHLM1 has variable age of onset, ranging from the prenatal period to adulthood, with onset of symptoms in childhood or early adulthood being most common. Clinical features of BTHLM1 include slowly progressive proximal muscle weakness and variable joint contractures. Ankles, elbows, and long finger flexors are the most commonly affected joints. Type VI collagenopathies can be associated with skin findings, including hypertrophic and keloid scarring. Intelligence is typically normal in affected individuals.

Individuals with COL12A1-related disorders have been described with a blended muscle and connective tissue presentation that is reminiscent of Type VI collagenopathies ranging from severe Ullrich congenital muscular dystrophy to milder Bethlem-like myopathies. Clinical features include congenital muscle weakness, distal joint laxity, proximal contractures, feeding difficulties and kyphoscoliosis, and mild facial dysmorphia.

This test covers three genes associated with type VI collagenopathies, including COL6A2, which causes an estimated 44% of cases; COL6A1, which accounts for 38% of cases; and COL6A3, which accounts for the remaining 18% of cases.

Type VI collagenopathies can be inherited in an autosomal dominant or autosomal recessive manner. BTHLM1 is typically an autosomal dominant condition while UCMD1 is typically an autosomal recessive condition.

Likewise, BTHLM2 is typically an autosomal dominant condition while UCMD2 is typically an autosomal recessive condition

Individuals who carry a dominant pathogenic variant or two recessive pathogenic variants for a type VI collagenopathy are symptomatic. However, type VI collagenopathies are variable disorders, and some affected individuals may appear asymptomatic unless a careful clinical evaluation is performed.

The prevalence of BTHLM1 is approximately 1 in 100,000 and the prevalence of UCMD1 is approximately 1 in 1,000,000. Both conditions have been observed in a number of different ethnicities.

The clinical presentation of type VI collagenopathies can be variable. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression or inform recurrence risk.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
COL12A1 NM_004370.5
COL6A1 NM_001848.2
COL6A2 NM_001849.3
COL6A3 NM_004369.3