Invitae Comprehensive Myopathy Panel

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  • Test code: 03361
  • 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
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Test description

The Invitae Comprehensive Myopathy Panel analyzes up to 51 genes associated with inherited myopathies. Myopathies are a heterogeneous group of neuromuscular disorders characterized by weakness due to muscle dysfunction. Age of onset, symptom severity and histopathological findings are variable between different forms of myopathies. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of myopathy.

Given the clinical overlap between different types of myopathy, comprehensive testing allows for more efficient evaluation of multiple conditions based on a single indication for testing. Identification of the molecular basis of disease can be useful in confirming a diagnosis, predicting disease course, and informing recurrence risk.

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Primary panel (49 genes)

ACTA1 ANO5 ATP2A1 BAG3 BIN1 CACNA1S CAV3 CCDC78 CFL2 CNTN1 COL6A1 COL6A2 COL6A3 CPT2 CRYAB DES DNAJB6 DNM2 DYSF FHL1 FKBP14 FLNC GNE KBTBD13 KCNJ2 KLHL40 KLHL41 LDB3 LMNA LMOD3 MATR3 MEGF10 MTM1 MYH7 MYL2 MYOT NEB RYR1 SCN4A SEPN1 SQSTM1 STAC3 STIM1 TIA1 TNNT1 TPM2 TPM3 TTN VCP

NEB: This assay detects the exon 55 deletion found in Ashkenazi Jewish individuals in association with nemaline myopathy. Exons 82-105 contain a large triplicated region. Deletion/duplication analysis excludes this region. Sequence changes in this region can be detected, but this assay cannot determine which of the three repeat units is affected (and zygosity is often ambiguous). All variants in this region are reported relative to the exon 82-89 repeat.
RYR1: Deletion/duplication analysis is not offered for exons 48 or 49.
SEPN1: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.
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).

Add-on preliminary-evidence gene (2 genes)

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 genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

COL12A1 MYF6

Alternative tests to consider

In some cases, myopathies may have overlapping features with congenital muscular dystrophies. If a congenital muscular dystrophy is suspected, clinicians may consider the Invitae Congenital Muscular Dystrophy Panel, or the Invitae Comprehensive Muscular Dystrophy panel. Myopathies may also have nonspecific or overlapping features with other neuromuscular disorders, in which case clinicians may consider Invitae’s Comprehensive Neuromuscular panel, which includes genes associated with myopathies, muscular dystrophies, and congenital myasthenic syndrome.

Inherited myopathies are a heterogeneous group of neuromuscular disorders, which are characterized by skeletal muscle dysfunction leading to muscle weakness of varying severity. Certain subtypes of myopathy are also commonly associated with cardiac disease. Other symptoms associated with myopathies may include muscle cramps, stiffness, and/or spasms, joint contractures, and respiratory insufficiency. Age of onset can vary from the prenatal period to adulthood depending on the specific subtype and the causative gene. Some myopathies can be divided into subtypes based on specific muscle biopsy findings, such as central cores, central nuclei, fiber-type disproportion, multiminicores, and nemaline bodies.

GeneInheritanceAssociated myopathies
Autosomal dominantAutosomal recessiveX-linked
ACTA1 nemaline myopathy-3, congenital fiber-type disproportion
ANO5 Miyoshi muscular dystrophy-3
ATP2A1 Brody myopathy
BAG3 myofibrillar myopathy-6
BIN1 centronuclear myopathy-2
CACNA1S hypokalemic periodic paralysis, type 1
CAV3 distal myopathy, Tateyama type
CCDC78 centronuclear myopathy-4
CFL2 nemaline myopathy-7
CNTN1 Compton-North congenital myopathy
COL12A1* Bethlem myopathy-2, Ullrich congenital muscular dystrophy-2
COL6A1 Bethlem myopathy-1, Ullrich congenital muscular dystrophy-1
COL6A2 Bethlem myopathy-1, Ullrich congenital muscular dystrophy-1
COL6A3 Bethlem myopathy-1, Ullrich congenital muscular dystrophy-1
CPT2 carnitine palmitoyltransferase II (CPT II) deficiency
CRYAB myofibrillar myopathy-2, CRYAB-associated fatal infantile hypertonic myofibrillar myopathy
DES myofibrillar myopathy-1
DNAJB6 distal myopathy, myofibrillar myopathy
DNM2 centronuclear myopathy
DYSF Miyoshi muscular dystrophy-1
FHL1 myofibrillar myopathy
FKBP14 Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss
FLNC distal myopathy-4, myofibrillar myopathy-5
GNE GNE-related myopathy
KBTBD13 nemaline myopathy-6
KCNJ2 Andersen-Tawil syndrome
KLHL40 nemaline myopathy-8
KLHL41 nemaline myopathy-9
LDB3 myofibrillar myopathy-4
LMNA congenital fiber-type disproportion
LMOD3 nemaline myopathy-10
MATR3 distal myopathy-2
MEGF10 early-onset myopathy with minicores, areflexia, respiratory distress, and dysphagia
MTM1 X-linked centronuclear myopathy
MYF6* centronuclear myopathy-3
MYH7 Laing distal myopathy, myosin storage myopathy, congenital fiber-type disproportion
MYL2 light-chain myopathy
MYOT myofibrillar myopathy-3
NEB nemaline myopathy-2
RYR1 central core disease, centronuclear myopathy, congenital fiber-type disproportion, multiminicore disease
SCN4A hyperkalemic/hypokalemic periodic paralysis.  
SEPN1 multiminicore disease
SQSTM1 Paget disease of the bone, distal myopathy
STAC3 Native American myopathy
STIM1 tubular aggregate myopathy, Stormoken syndrome
TIA1 Welander distal myopathy
TNNT1 nemaline myopathy-4
TPM2 congenital fiber-type disproportion, nemaline myopathy
TPM3 congenital fiber-type disproportion, nemaline myopathy-1
TTN centronuclear myopathy, tibial muscular dystrophy
VCP inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

*Preliminary-evidence gene

The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. For each condition, the table below shows the percentage of clinical cases in which a pathogenic variant is expected to be identified through analysis of the genes listed. This panel also includes other genes that have been identified as causes of myopathy, although the exact contribution of these genes to the overall detection rate is not known and again, may be dependent on the clinical presentation of the patient. Testing of all currently known causative myopathy genes does not result in identification of a genetic cause in 100% of affected individuals.

Sensitivity by clinical conditionGenes
90% of central core disease (PMID: 20301565) RYR1
70% of centronuclear myopathy (PMID: 25957634) DNM2, MTM1, RYR1, TTN
up to 66% of congenital fiber-type disproportion (PMID: 20301436) ACTA1, RYR1, TPM3
~100% of Laing distal myopathy (PMID: 20301606) MYH7
70% of myofibrillar myopathy (PMID: 20301672) BAG3, CRYAB, DES, DNAJB6, FHL1, FLNC, LDB3, MYOT
30-50% of multiminicore disease (PMID: 20301467) SEPN1
up to 80% of nemaline myopathy (PMID: 20301465) ACTA1, NEB, TPM2, TPM3
up to 100% of type VI collagenopathies (PMID: 20301676) COL6A1, COL6A2, COL6A3

Inherited myopathies can be associated with different inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked. Some genes are associated with both autosomal dominant and autosomal recessive neuromuscular disorders.

Incomplete penetrance has been observed for some forms of myopathy, including congenital fiber-type disproportion, nemaline myopathy, myofibrillar myopathy, and distal myopathy. Other forms of myopathy such as central core disease, Bethlem myopathy, Ullrich congenital muscular dystrophy, and X-linked centronuclear myopathy are thought to be close to 100% penetrant. Some forms of myopathy do not present until late adulthood, which makes determination of penetrance difficult.

Most forms of myopathy are rare, and the overall prevalence is unknown. The prevalence of congenital forms of myopathy in the United States is estimated to be 1 in 26,000.

The clinical spectrum of myopathies is variable. Genetic testing may confirm a suspected diagnosis or rule out other disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform recurrence risk.

  1. Amburgey, K, et al. Prevalence of congenital myopathies in a representative pediatric united states population. Ann. Neurol. 2011; 70(4):662-5. PMID: 22028225
  2. Aoki, M. Dysferlinopathy. 2004 Feb 05. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301480
  3. Colombo, I, et al. Congenital myopathies: Natural history of a large pediatric cohort. Neurology. 2015; 84(1):28-35. PMID: 25428687
  4. Das, S, et al. X-Linked Centronuclear Myopathy. 2002 Feb 25. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301605
  5. DeChene, ET, et al. Congenital Fiber-Type Disproportion. 2007 Jan 12. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301436
  6. Dimachkie, MM, Barohn, RJ. Distal myopathies. Neurol Clin. 2014; 32(3):817-42, x. PMID: 25037092
  7. Gorokhova, S, et al. Clinical massively parallel sequencing for the diagnosis of myopathies. Rev. Neurol. (Paris). 2015; 171(6-7):558-71. PMID: 26022190
  8. Lampe, AK, et al. Collagen Type VI-Related Disorders. 2004 Jun 25. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301676
  9. M, King, W, Kissel, JT. Multidisciplinary approach to the management of myopathies. Continuum (Minneap Minn). 2013; 19(6 Muscle Disease):1650-73. PMID: 24305452
  10. Maggi, L, et al. Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. Neuromuscul. Disord. 2013; 23(3):195-205. PMID: 23394784
  11. Malicdan, MCV, Nishino, I. Central Core Disease. 2007 May 16. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301565
  12. North, KN, Ryan, MM. Nemaline Myopathy. 2002 Jun 19. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301465
  13. Stamm, DS, et al. Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. Am. J. Med. Genet. A. 2008; 146A(14):1832-41. PMID: 18553514

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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACTA1 NM_001100.3
ANO5 NM_213599.2
ATP2A1 NM_173201.3
BAG3 NM_004281.3
BIN1 NM_139343.2
CACNA1S NM_000069.2
CAV3 NM_033337.2
CCDC78 NM_001031737.2
CFL2 NM_021914.7
CNTN1 NM_001843.3
COL12A1 NM_004370.5
COL6A1 NM_001848.2
COL6A2 NM_001849.3
COL6A3 NM_004369.3
CPT2 NM_000098.2
CRYAB NM_001885.2
DES NM_001927.3
DNAJB6 NM_058246.3
DNM2 NM_001005360.2
DYSF NM_003494.3
FHL1 NM_001449.4, NM_001159702.2
FKBP14 NM_017946.3
FLNC NM_001458.4
GNE NM_001128227.2
KBTBD13 NM_001101362.2
KCNJ2 NM_000891.2
KLHL40 NM_152393.3
KLHL41 NM_006063.2
LDB3 NM_001080116.1, NM_001171610.1
LMNA NM_170707.3
LMOD3 NM_198271.4
MATR3 NM_199189.2
MEGF10 NM_032446.2
MTM1 NM_000252.2
MYF6 NM_002469.2
MYH7 NM_000257.3
MYL2 NM_000432.3
MYOT NM_006790.2
NEB* NM_001271208.1
RYR1* NM_000540.2
SCN4A NM_000334.4
SEPN1* NM_020451.2
SQSTM1 NM_003900.4
STAC3 NM_145064.2
STIM1 NM_003156.3
TIA1 NM_022173.2
TNNT1 NM_003283.5
TPM2 NM_003289.3
TPM3 NM_152263.3
TTN* NM_001267550.2
VCP NM_007126.3

NEB: This assay detects the exon 55 deletion found in Ashkenazi Jewish individuals in association with nemaline myopathy. Exons 82-105 contain a large triplicated region. Deletion/duplication analysis excludes this region. Sequence changes in this region can be detected, but this assay cannot determine which of the three repeat units is affected (and zygosity is often ambiguous). All variants in this region are reported relative to the exon 82-89 repeat.
RYR1: Deletion/duplication analysis is not offered for exons 48 or 49.
SEPN1: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.
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).