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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 EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Comprehensive Myopathy Panel

Test description

The Invitae Comprehensive Myopathy Panel analyzes genes that are associated with inherited myopathies, a heterogeneous group of neuromuscular conditions characterized by weakness due to muscle dysfunction. The genetic heterogeneity associated with these conditions can make it difficult to use phenotype as the sole criterion to select a definitive cause. These genes were curated based on the available evidence to date in order to provide analysis for inherited myopathies. Given the clinical overlap of inherited myopathies, broad panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication. Some genes in this test may also be associated with additional unrelated disorders, which are not included in the list of disorders tested. Genetic testing of these genes may help confirm a clinical diagnosis, predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.

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Primary panel (71 genes)

ACTA1 ADSSL1 AMPD1 ANO5 ATP2A1 BAG3 BIN1 CACNA1S CASQ1 CAV3 CCDC78 CFL2 CLCN1 CNTN1 COL12A1 COL6A1 COL6A2 COL6A3 CPT2 CRYAB DES DNAJB6 DNM2 DYSF FHL1 FKBP14 FLNC GNE GYG1 GYS1 HACD1 HNRNPA2B1 ISCU KBTBD13 KCNJ2 KLHL40 KLHL41 LAMP2 LDB3 LMNA LMOD3 MAP3K20 MATR3 MEGF10 MICU1 MTM1 MYH2 MYH7 MYL2 MYO18B MYOT MYPN NEB ORAI1 PYROXD1 RYR1 SCN4A SELENON SPEG SQSTM1 STAC3 STIM1 TAZ TIA1 TK2 TNNT1 TPM2 TPM3 TTN VCP VMA21

Add-on Preliminary-evidence Genes for Myopathy (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.

KLHL9 MTMR14

Broad disorders tested:

  • Central Core Disease
  • Centronuclear Myopathy
  • Congenital Fiber Type Disproportion
  • Congenital Myopathy
  • Multiminicore Disease
  • Myofibrillar Myopathy
  • Nemaline Myopathy
  • Type VI Collagenopathies

Individual disorders tested

  • Centronuclear Myopathy (CNM) Subtypes
  • centronuclear myopathy 2 (CNM2)
  • centronuclear myopathy 4 (CNM4)
  • centronuclear myopathy 5 (CNM5)
  • centronuclear myopathy 6 (CNM6)
  • DNM2-associated centronuclear myopathy (DNM2-CNM)
  • TTN-related centronuclear myopathy
  • X-linked centronuclear myopathy (XLCNM)

  • Myofibrillar Myopathy (MFM) Subtypes
  • myofibrillar myopathy 1 (MFM1)
  • myofibrillar myopathy 2 (MFM2)
  • myofibrillar myopathy 3 (MFM3)
  • myofibrillar myopathy 4 (MFM4)
  • myofibrillar myopathy 5 (MFM5)
  • myofibrillar myopathy 6 (MFM6)
  • myofibrillar myopathy 8 (MFM8)
  • Nemaline Myopathy (NEM) Subtypes
  • nemaline myopathy 1 (NEM1), congenital myopathy with fiber-type disproportion (CFTD)
  • nemaline myopathy 2 (NEM2)
  • nemaline myopathy 3 (NEM3), congenital myopathy with fiber-type disproportion (CFTD)
  • nemaline myopathy 4 (NEM4), CAP myopathy 2 (CAPM2), congenital myopathy with fiber-type disproportion (CFTD)
  • nemaline myopathy 5 (NEM5)
  • nemaline myopathy 6 (NEM6)
  • nemaline myopathy 7 (NEM7)
  • nemaline myopathy 8 (NEM8)
  • nemaline myopathy 9 (NEM9)
  • nemaline myopathy 10 (NEM10)
  • nemaline myopathy 11 (NEM11)
  • Type VI Collagenopathies
  • Bethlem myopathy 1 (BTHLM1), Ullrich congenital muscular dystrophy 1 (UCMD1)
  • Bethlem myopathy 2 (BTHLM2), Ullrich congenital muscular dystrophy 2 (UCMD2)
  • Other Disorders
  • Andersen-Tawil syndrome/long QT syndrome (LQTS), type 7
  • Barth Syndrome (BTHS), 3-methylglutaconic aciduria type II
  • Brody myopathy
  • CACNA1S-related congenital myopathy
  • carnitine palmitoyltransferase II (CPTII or CPT2) deficiency
  • CAV3-related distal myopathy, caveolinopathies
  • central core disease (CCD), congenital myopathy with fiber-type disproportion (CFTD), multiminicore disease (MmD), centronuclear myopathy (CNM)
  • Compton-North congenital myopathy (MYPCN)
  • Danon disease
  • distal myopathy 2 (MPD2)
  • distal myopathy 4 (MPD4)
  • distal myopathy 5 (MPD5)
  • distal myopathy with anterior tibial onset (DMAT), dysferlinopathies
  • DNAJB6-related distal myopathy
  • early-onset MYL2-associated light chain myopathy
  • early-onset myopathy, areflexia, respiratory distress and dysphasia (EMARDD)
  • Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss (EDSKMH)
  • glycogen synthase deficiency, muscle type (GSD 0b, muscle form)
  • GNE-related myopathy
  • HACD1-related congenital myopathy
  • hereditary myopathy with early respiratory failure (HMERF)
  • hereditary myopathy with lactic acidosis (HML)
  • inclusion body myopathy type 3 (MYPOP)
  • inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 (IBMPFD1)
  • inclusion body myopathy with early-onset Paget disease, with or without frontotemporal dementia 2 (IBMPFD2)
  • Klippel-Feil syndrome with myopathy and facial dysmorphism
  • mitochondrial DNA depletion syndrome 2 (MTDPS2)
  • muscle AMP deaminase deficiency (MMDD)
  • myopathy with extrapyramidal signs
  • myosin storage myopathy (MSMA), scapuloperoneal myopathy (SPMM), Laing distal myopathy (MPD1), congenital myopathy with fiber-type disproportion (CFTD)
  • myotonia congenita
  • Paget disease of bone (PDB3)
  • paramyotonia congenita
  • polyglucosan body myopathy 2 (PGBM2), glycogen storage disease XV (GSD XV)
  • reducing body myopathy (RBM), scapuloperoneal myopathy
  • rigid spine muscular dystrophy 1 (RSMD1), congenital myopathy with fiber-type disproportion (CFTD)
  • STAC3-related congenital myopathy
  • tubular aggregate myopathy 1 (TAM1), Stormorken (STRMK) syndrome
  • tubular aggregate myopathy 2 (TAM2)
  • vacuolar myopathy with CASQ1 aggregates
  • Welander distal myopathy (WDM)
  • X-linked myopathy with excessive autophagy (XMEA)

To view the complete clinical description of this panel, click here.

Myopathies can be inherited in an autosomal dominant, autosomal recessive or X-linked pattern.

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
ACTA1 NM_001100.3
ADSSL1 NM_199165.2
AMPD1 NM_000036.2
ANO5 NM_213599.2
ATP2A1 NM_173201.3
BAG3 NM_004281.3
BIN1 NM_139343.2
CACNA1S NM_000069.2
CASQ1 NM_001231.4
CAV3 NM_033337.2
CCDC78 NM_001031737.2
CFL2 NM_021914.7
CLCN1 NM_000083.2
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
FKBP14 NM_017946.3
FLNC* NM_001458.4
GNE NM_001128227.2
GYG1 NM_004130.3
GYS1 NM_002103.4
HACD1 NM_014241.3
HNRNPA2B1 NM_031243.2
ISCU NM_213595.3
KBTBD13 NM_001101362.2
KCNJ2 NM_000891.2
KLHL40 NM_152393.3
KLHL41 NM_006063.2
KLHL9 NM_018847.3
LAMP2 NM_002294.2
LDB3 NM_001080116.1; NM_001171610.1,NM_007078.3
LMNA NM_170707.3
LMOD3 NM_198271.4
MAP3K20 NM_016653.2
MATR3 NM_199189.2
MEGF10 NM_032446.2
MICU1 NM_006077.3
MTM1 NM_000252.2
MTMR14 NM_022485.4
MYH2 NM_017534.5
MYH7 NM_000257.3
MYL2 NM_000432.3
MYO18B NM_032608.6
MYOT NM_006790.2
MYPN NM_032578.3
NEB* NM_001271208.1
ORAI1 NM_032790.3
PYROXD1 NM_024854.3
RYR1 NM_000540.2
SCN4A NM_000334.4
SELENON* NM_020451.2
SPEG NM_005876.4
SQSTM1 NM_003900.4
STAC3 NM_145064.2
STIM1 NM_003156.3
TAZ NM_000116.4
TIA1 NM_022173.2
TK2 NM_004614.4
TNNT1 NM_003283.5
TPM2 NM_003289.3
TPM3* NM_152263.3
TTN* NM_001267550.2
VCP NM_007126.3
VMA21 NM_001017980.3

FLNC: Deletion/duplication analysis is not offered for exon 47. Sensitivity and specificity for single nucleotide variants, insertions and deletions in exons 47-48 may be reduced due to the presence of segmental duplications overlapping the region.
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. Deletion/duplication analysis is not offered for exons 82-105. NEB variants in this region with no evidence towards pathogenicity are not included in this report, but are available upon request.
SELENON: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.
TPM3: Deletion/duplication analysis is not offered for exon 10.
TTN: Exons 45-46, 147, 149, 158-201, 212-216 (NM_001267550.2) are excluded from analysis. TTN variants are reported in the primary report based on functional effect and/or location. A complete list of variants of uncertain significance, likely benign and benign variants in TTN is available upon request. 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).