Test ID MUPAN Comprehensive Neuromuscular Gene Panel, Varies
Ordering Guidance
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH/ Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Forms
1. New York Clients-Informed consent is required.
Document on the request form or electronic order that a copy is on file.
The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Molecular Genetics: Neurology Patient Information
3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.
Useful For
Establishing a molecular diagnosis for patients with a neuromuscular disorder
Identifying variants within genes known to be associated with neuromuscular disorders allowing for predictive testing of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 215 genes associated with neuromuscular disorders: ABHD5, ACAD9, ACADM, ACADS, ACADVL, ACTA1, ADSS1, AGK, AGL, AGRN, ALDOA, ALG14, ALG2, ANO5, ASAH1, ASCC1, ATP1A2, ATP2A1, B3GALNT2, B4GAT1, BAG3, BIN1, BVES, CACNA1S, CAPN3, CASQ1, CAV3, CAVIN1, CFL2, CHAT, CHCHD10, CHKB, CHRNA1, CHRNB1, CHRND, CHRNE, CLCN1, COL12A1, COL13A1, COL6A1, COL6A2, COL6A3, COLQ, COQ2, COQ4, COQ6, COQ8A, COQ9, CPT2, CRPPA, CRYAB, CTDP1, DAG1, DES, DGUOK, DMD, DNA2, DNAJB6, DNM2, DOK7, DPAGT1, DPM1, DPM2, DPM3, DYSF, EMD, ENO3, ETFA, ETFB, ETFDH, FAM111B, FBXL4, FDX2, FHL1, FKBP14, FKRP, FKTN, FLAD1, FLNC, GAA, GBE1, GFER, GFPT1, GMPPB, GNE, GOSR2, GYG1, GYS1, HADHA, HADHB, HNRNPA1, HNRNPA2B1, HNRNPDL, HRAS, INPP5K, ISCU, ITGA7, JAG2, KBTBD13, KCNJ2, KLHL40, KLHL41, KY, LAMA2, LAMB2, LAMP2, LARGE1, LDB3, LDHA, LMNA, LMOD3, LPIN1, LRP4, MAP3K20, MATR3, MB, MEGF10, MGME1, MICU1, MRPS25, MSTO1, MTM1, MTO1, MUSK, MYBPC1, MYH2, MYH7, MYMK, MYOT, MYPN, NEB, OPA1, ORAI1, PAX7, PDSS1, PDSS2, PFKM, PGAM2, PGK1, PGM1, PHKA1, PLEC, PNPLA2, PNPLA8, POGLUT1, POLG, POLG2, POMGNT1, POMGNT2, POMK, POMT1, POMT2, PREPL, PRKAG2, PUS1, PYGM, PYROXD1, RAPSN, RBCK1, RNASEH1, RRM2B, RXYLT1, RYR1, SCN4A, SDHA, SELENON, SGCA, SGCB, SGCD, SGCG, SIL1, SLC18A3, SLC22A5, SLC25A1, SLC25A20, SLC25A3, SLC25A4, SLC25A42, SLC5A7, SPEG, SQSTM1, STAC3, STIM1, SUCLA2, SUCLG1, SUN1, SUN2, SYNE1, SYT2, TANGO2, TAZ (TAFAZZIN), TBCD, TCAP, TFG, TIA1, TK2, TMEM43, TMEM65, TNNT1, TNPO3, TOR1AIP1, TPM2, TPM3, TRAPPC11, TRIM32, TRIP4, TSFM, TTC19, TTN, TWNK, UBA1, VAMP1, VCP, VMA21, YARS2. SMN1 exon 7 and SMN2 exon 7 copy number are determined by droplet digital polymerase chain reaction. See Targeted Genes and Methodology Details for Comprehensive Neuromuscular Gene Panel and Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for neuromuscular disorders.
Method Name
Sequence Capture and Next-Generation Sequencing (NGS), Polymerase Chain Reaction (PCR), Sanger Sequencing, and Dosage Analysis by Droplet Digital Polymerase Chain Reaction (ddPCR)
Reporting Name
Neuromuscular Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Neuromuscular disorders are a heterogeneous group of diseases that arise from nerve, muscle, or neuromuscular junction dysfunction. Onset ranges from in utero to old age, but mostly they affect infants, children, and teenagers. While some neuromuscular disorders are acquired, the vast majority are genetic. Diagnosis of neuromuscular disorders involves clinical presentation, electromyography , muscle and nerve biopsy, and biochemical and genetic testing. This panel includes genes associated with muscular dystrophy, myopathy, rhabdomyolysis, congenital myasthenic syndrome, and skeletal muscular channelopathy disorders.
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Cautions
Clinical Correlations:
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.
To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors at 800-533-1710.
Technical Limitations:
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.
This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.
Deletion/Duplication Analysis:
This analysis targets single and multi-exon deletions/duplications; however, in some instances, single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.
This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.
Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Comprehensive Neuromuscular Gene Panel for the most up to date list of genes included in this test. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reclassification of Variants:
At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report.
Variant Evaluation:
Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(1) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.
Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.
Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be reported.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424
2. Laing NG: Genetics of neuromuscular disorders. Crit Rev Clin Lab Sci. 2012 Mar-Apr;49(2):33-48
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Comprehensive Neuromuscular Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)
Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
Droplet digital PCR is performed for detection and quantification of SMN1 exon 7 and SMN2 exon 7 associated with spinal muscular atrophy.
Genes analyzed:
ABHD5, ACAD9, ACADM, ACADS, ACADVL, ACTA1, ADSS1, AGK, AGL, AGRN, ALDOA, ALG14, ALG2, ANO5, ASAH1, ASCC1, ATP1A2, ATP2A1, B3GALNT2, B4GAT1, BAG3, BIN1, BVES, CACNA1S, CAPN3, CASQ1, CAV3, CAVIN1, CFL2, CHAT, CHCHD10, CHKB, CHRNA1, CHRNB1, CHRND, CHRNE, CLCN1, COL12A1, COL13A1, COL6A1, COL6A2, COL6A3, COLQ, COQ2, COQ4, COQ6, COQ8A, COQ9, CPT2, CRPPA, CRYAB, CTDP1, DAG1, DES, DGUOK, DMD, DNA2, DNAJB6, DNM2, DOK7, DPAGT1, DPM1, DPM2, DPM3, DYSF, EMD, ENO3, ETFA, ETFB, ETFDH, FAM111B, FBXL4, FDX2, FHL1, FKBP14, FKRP, FKTN, FLAD1, FLNC, GAA, GBE1, GFER, GFPT1, GMPPB, GNE, GOSR2, GYG1, GYS1, HADHA, HADHB, HNRNPA1, HNRNPA2B1, HNRNPDL, HRAS, INPP5K, ISCU, ITGA7, JAG2, KBTBD13, KCNJ2, KLHL40, KLHL41, KY, LAMA2, LAMB2, LAMP2, LARGE1, LDB3, LDHA, LMNA, LMOD3, LPIN1, LRP4, MAP3K20, MATR3, MB, MEGF10, MGME1, MICU1, MRPS25, MSTO1, MTM1, MTO1, MUSK, MYBPC1, MYH2, MYH7, MYMK, MYOT, MYPN, NEB, OPA1, ORAI1, PAX7, PDSS1, PDSS2, PFKM, PGAM2, PGK1, PGM1, PHKA1, PLEC, PNPLA2, PNPLA8, POGLUT1, POLG, POLG2, POMGNT1, POMGNT2, POMK, POMT1, POMT2, PREPL, PRKAG2, PUS1, PYGM, PYROXD1, RAPSN, RBCK1, RNASEH1, RRM2B, RXYLT1, RYR1, SCN4A, SDHA, SELENON, SGCA, SGCB, SGCD, SGCG, SIL1, SLC18A3, SLC22A5, SLC25A1, SLC25A20, SLC25A3, SLC25A4, SLC25A42, SLC5A7, SPEG, SQSTM1, STAC3, STIM1, SUCLA2, SUCLG1, SUN1, SUN2, SYNE1, SYT2, TANGO2, TAZ (TAFAZZIN), TBCD, TCAP, TFG, TIA1, TK2, TMEM43, TMEM65, TNNT1, TNPO3, TOR1AIP1, TPM2, TPM3, TRAPPC11, TRIM32, TRIP4, TSFM, TTC19, TTN, TWNK, UBA1, VAMP1, VCP, VMA21, and YARS2
Day(s) Performed
Varies
Report Available
28 to 42 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81443
NY State Approved
YesTesting Algorithm
For more information see Neuromuscular Myopathy Testing Algorithm