MyoGene Panel (43 Genes) Test Details
Inherited muscle diseases are a clinically and genetically heterogeneous group of disorders that typically present with hypotonia, muscle weakness, and delayed motor milestones, which may be accompanied with respiratory insufficiency and/or feeding difficulty. Familial inheritance is common and can involve autosomal recessive, autosomal dominant, or X-linked inheritance. These diseases can be broadly divided into muscular dystrophies (characterized by progressive muscle weakness with pathological evidence of continuous muscle degeneration and regeneration) and congenital myopathies that often present at birth or in childhood with a generally nonprogressive course of disease.
Available Myopathy Panel Tests
MyoGene Panel - 43 genes
- Muscular Dystrophy (LGMD/EDMD) Panel - 25 genes§
- Congenital Myopathy Panel - 14 genes§
- Nemaline Myopathy Panel - 7 genes§
- Myotubular/Centronuclear Myopathy Panel - 5 genes§
- Myofibrillar Myopathy Panel - 8 genes§
§Optional reflex to remaining genes
** All patients with a suspected diagnosis of DMD/BMD should have DMD sequencing and deletion/duplication testing performed prior to ordering the MyoGene Panel due to the decreased ability of NGS to detect single exon CNVs. **
Read More for expanded gene table.Read More...
|ACTA1||Actin, Alpha, Skeletal Muscule 1||102610||1q42.13|
|BAG3||BCL2-Associated Athanogene 3||603883||10q26.11|
|BIN1||Briding Integrator 1||601248||2q14.3|
|DAG1||Dystrophin-Associated Glycoprotein 1||128239||3p21.31|
|DNAJB6||DNAJ/HSP40 Homolog, Subfamily B, Member 6||611332||7q36.3|
|FHL1||Four-and-a-half Lim Domains 1||300163||Xq26.3|
|ISPD||Isoprenoid Synthase Domain-Containing Protein||614631||7p21.2|
|LDB3||Lim Domain-Binding 3||605906||10q23.2|
|MYH7||Myosin, Heavy Chain 7, Cardiac Muscle, Beta||160760||14q11.2|
|POMGNT1||Protein O-Mannose Beta-1,2-N-Acetylglucosaminyltransferase||606822||1p34.1|
|POMT1||Protein O-Mannosyltransferase 1||607423||9q34.13|
|POMT2||Protein O0Mannosyltransferase 2||607439||14q24.3|
|RYR1||Ryanodine Receptor 1||180901||19q13.2|
|SEPN1||Selenoprotein N, 1||606210||1p36.11|
|TNNT1||Troponin T1, Skeletal, Slow||191041||19q13.42|
|TRIM32||Tripartite Motif-Containing Protein 32||602290||9q33.1|
The MyoGene Panel is best suited for individuals who already have exhausted current testing options or those whose clinical diagnosis is not yet clear and may help shorten the “diagnostic odyssey.” While the MyoGene Panel offers comprehensive testing for multiple forms of myopathy, there is a higher likelihood of finding novel variants, which may be more difficult to interpret if it is found in a gene that is not (yet) known to cause the individual’s disease.
This test is performed by next generation sequencing using Agilent SureSelect capture followed by sequencing of the coding regions and splice sites using Illumina sequencing technologies. Variant calls are generated using the Burrows-Wheeler Aligner followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or an alternate assay. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions that could affect gene expression, aside from the splice junctions, and a few exons have been excluded due to technical difficulties. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.
The detection rate of the MyoGene Panel is dependent on the clinical diagnosis and is expected to be approximately 90% for childhood-onset and 35% for adult-onset LGMD (GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1408/), ~35% for EDMD (GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1436/), ~25% for congenital myopathy (Amburgey 2011: PubMed ID 22028225), ~75% for nemaline myopathy (GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1288/; Malfatti 2014: PubMed ID 24725366), approximately 80% for patients diagnosed with myotubular or centronuclear myopathy (Biancalana 2012: PubMed ID 22617344), and ~40-45% for myofibrillar myopathy (GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1499/).