• Test code: 03364
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Centronuclear Myopathy Panel

Test description

The Invitae Centronuclear Myopathy Panel analyzes up to seven genes associated with centronuclear myopathy (CNM), a disorder characterized by hypotonia and progressive skeletal muscle weakness. Muscle biopsies typically show displacement of nuclei to the center of muscle cells. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of centronuclear myopathy.

Given that centronuclear myopathy is a heterogeneous disorder, identification of the underlying genetic cause can help predict patient outcome and inform recurrence risk.

Order test

Primary panel (6 genes)
Add-on Preliminary-evidence Gene for Centronuclear Myopathy (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our “(external) Preliminary-evidence genes”:/preliminary-evidence/ page to learn more.


Alternative tests to consider

For a broader analysis of genes associated with congenital myopathies, clinicians may consider the Invitae Congenital Myopathy Panel, or the Invitae Comprehensive Myopathy Panel. These broader panels can be ordered at no additional charge.

Centronuclear myopathy (CNM) is a congenital myopathy of intermediate severity that is generally characterized by hypotonia and progressive skeletal muscle weakness. Age of onset is variable and ranges from prenatal- or infantile-onset to adult-onset forms. Some forms of CNM involve respiratory issues and/or predominately facial muscle involvement. The principle muscle biopsy finding early in life consists of several centrally located nuclei, but other features, including type 1 muscle fiber predominance or fiber-type disproportion and cores, may also be noted over time. The most severe form of CNM is associated with the X-linked gene MTM1. Affected males with MTM1-related CNM have profound hypotonia, muscle weakness, and respiratory insufficiency at birth.

Individuals with RYR1-related CNM may be at increased risk for malignant hyperthermia susceptibility (MHS), a pharmacogenetic disorder that is characterized by susceptibility to uncontrolled skeletal muscle hypermetabolism after exposure to certain volatile anesthetics.

Gene Inheritance Typical age of onset Respiratory issues typical? Cardiac issues typical?
Autosomal dominant Autosomal Recessive X-linked
BIN1 Early childhood
CCDC78 Early childhood (limited data available) Unknown (limited data available) Unknown (limited data available)
DNM2 Childhood or adolescence
MTM1 Prenatal or at birth
MYF6 Childhood (limited data available) Unknown (limited data available) Unknown (limited data available)
RYR1 At birth
TTN Childhood

In a cohort of 54 individuals with CNM, 28% were identified to have pathogenic variants in MTM1, 11% had variants in DNM2, and 6% had variants in RYR1. Among individuals with adult-onset CNM, pathogenic variants in DNM2 are typically most common. Pathogenic variants in the BIN1 gene may account for up to 25% of families with adult-onset CNM for whom autosomal recessive inheritance is suspected. This panel also includes other genes that have been identified as causes of CNM, although the exact contribution of these genes to the overall detection rate is not known and is dependent on the clinical presentation of the patient.

CNM associated with the CCDC78, DNM2, and MYF6 genes is inherited in an autosomal dominant pattern. RYR1- and TTN-associated CNMs are inherited in an autosomal recessive pattern. BIN1-associated CNM is typically inherited in an autosomal recessive pattern, though cases of autosomal dominant inheritance have also been reported. MTM1-associated CNM is an X-linked condition.

MTM1-associated CNM is considered to be 100% penetrant in males. Carrier females are typically asymptomatic, but they may exhibit symptoms in rare cases. Most other forms of CNM are rare, and penetrance estimates are not known.

CNM is a rare disorder whose overall prevalence is unknown. The incidence of MTM1-associated CNM is estimated at 2 per every 100,000 male births.

The clinical spectrum of centronuclear myopathies is broad. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and 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
BIN1 NM_139343.2
CCDC78 NM_001031737.2
DNM2 NM_001005360.2
MTM1 NM_000252.2
MYF6 NM_002469.2
RYR1 NM_000540.2
TTN* NM_001267550.2

TTN: Deletion/duplication and sequencing analysis is not offered for exons 153-155 (NM_133378.4). Variants are named relative to the NM_001267550.2 (meta) transcript, but only variants in the coding sequence and intronic boundaries of the clinically relevant NM_133378.4 (N2A) isoform are reported (PMID: 25589632).