Congenital Myopathy Panel
GTR Test Accession: Help GTR000506312.7
CAP
INHERITED DISEASEMUSCULOSKELETALNERVOUS SYSTEM ... View more
Last updated in GTR: 2021-01-19
Last annual review date for the lab: 2023-07-18 LinkOut
At a Glance
Diagnosis; Monitoring; Mutation Confirmation; ...
Actin accumulation myopathy; Autosomal dominant centronuclear myopathy; Autosomal recessive limb-girdle muscular dystrophy type 2J; ...
ACTA1 (1q42.13), ACTN2 (1q43), BAG3 (10q26.11), BIN1 (2q14.3), CCDC78 (16p13.3), ...
Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
The target population for this test is patients suspected of …
NM is inherited in an autosomal dominant or autosomal recessive …
Establish or confirm diagnosis
Ordering Information
Offered by: Help
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
  • Registered Nurse
CPT codes: Help
**AMA CPT codes notice
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order: Help
All samples should be shipped via overnight delivery at room temperature.
No weekend or holiday deliveries.
Label each specimen with the patient’s name, date of birth and date sample collected.
Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
No
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Conditions Help
Total conditions: 31
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 43
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 2
Method Category Help
Test method Help
Instrument *
Deletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Sequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
* Instrument: Not provided
Clinical Information
Test purpose: Help
Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Risk Assessment; Screening
Clinical validity: Help
NM is inherited in an autosomal dominant or autosomal recessive manner. In one series, approximately 20% of cases were autosomal recessive, approximately 30% autosomal dominant, and approximately 50% simplex (i.e., single occurrences in a family) representing heterozygosity for de novo dominant mutations or homozygosity for autosomal recessive mutations. Accurate recurrence … View more
View citations (29)
  • Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Pelin K, et al. Proc Natl Acad Sci U S A. 1999;96(5):2305-10. doi:10.1073/pnas.96.5.2305. PMID: 10051637.
  • MTM1 mutations in X-linked myotubular myopathy. Laporte J, et al. Hum Mutat. 2000;15(5):393-409. doi:10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R. PMID: 10790201.
  • Johnston JJ, Kelley RI, Crawford TO, Morton DH, Agarwala R, Koch T, Schäffer AA, Francomano CA, Biesecker LG. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet. 2000;67(4):814-21. doi:10.1086/303089. Epub 2000 Aug 21. PMID: 10952871.
  • Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. Kerst B, et al. Neuromuscul Disord. 2000;10(8):572-7. doi:10.1016/s0960-8966(00)00150-4. PMID: 11053684.
  • Nemaline myopathy: a clinical study of 143 cases. Ryan MM, et al. Ann Neurol. 2001;50(3):312-20. doi:10.1002/ana.1080. PMID: 11558787.
  • Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. Donner K, et al. Neuromuscul Disord. 2002;12(2):151-8. doi:10.1016/s0960-8966(01)00252-8. PMID: 11738357.
  • Characterization of mutations in fifty North American patients with X-linked myotubular myopathy. Herman GE, et al. Hum Mutat. 2002;19(2):114-21. doi:10.1002/humu.10033. PMID: 11793470.
  • Congenital myopathies and related disorders. Taratuto AL, et al. Curr Opin Neurol. 2002;15(5):553-61. doi:10.1097/00019052-200210000-00006. PMID: 12351999.
  • Genotype-phenotype correlations in X-linked myotubular myopathy. McEntagart M, et al. Neuromuscul Disord. 2002;12(10):939-46. doi:10.1016/s0960-8966(02)00153-0. PMID: 12467749.
  • X-linked myotubular and centronuclear myopathies. Pierson CR, et al. J Neuropathol Exp Neurol. 2005;64(7):555-64. doi:10.1097/01.jnen.0000171653.17213.2e. PMID: 16042307.
  • SEPN1: associated with congenital fiber-type disproportion and insulin resistance. Clarke NF, et al. Ann Neurol. 2006;59(3):546-52. doi:10.1002/ana.20761. PMID: 16365872.
  • Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet. 2007;80(1):162-7. doi:10.1086/510402. Epub 2006 Nov 14. PMID: 17160903.
  • Jungbluth H, Zhou H, Sewry CA, Robb S, Treves S, Bitoun M, Guicheney P, Buj-Bello A, Bönnemann C, Muntoni F. Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. Neuromuscul Disord. 2007;17(4):338-45. doi:10.1016/j.nmd.2007.01.016. Epub 2007 Mar 21. PMID: 17376685.
  • Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL, Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007;39(9):1134-9. doi:10.1038/ng2086. Epub 2007 Aug 05. PMID: 17676042.
  • Echaniz-Laguna A, Nicot AS, Carré S, Franques J, Tranchant C, Dondaine N, Biancalana V, Mandel JL, Laporte J. Subtle central and peripheral nervous system abnormalities in a family with centronuclear myopathy and a novel dynamin 2 gene mutation. Neuromuscul Disord. 2007;17(11-12):955-9. doi:10.1016/j.nmd.2007.06.467. Epub 2007 Sep 06. PMID: 17825552.
  • Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset. Bitoun M, et al. Ann Neurol. 2007;62(6):666-70. doi:10.1002/ana.21235. PMID: 17932957.
  • Compton AG, Albrecht DE, Seto JT, Cooper ST, Ilkovski B, Jones KJ, Challis D, Mowat D, Ranscht B, Bahlo M, Froehner SC, North KN. Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy. Am J Hum Genet. 2008;83(6):714-24. doi:10.1016/j.ajhg.2008.10.022. Epub 2008 Nov 20. PMID: 19026398.
  • Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1). Laing NG, et al. Hum Mutat. 2009;30(9):1267-77. doi:10.1002/humu.21059. PMID: 19562689.
  • DeChene ET, Kang PB, Beggs AH. Congenital Fiber-Type Disproportion – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2007 Jan 12 [updated 2013 Apr 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301436.
  • North KN, Ryan MM. Nemaline Myopathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2002 Jun 19 [updated 2015 Jun 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301465.
  • RYR1 mutations are a common cause of congenital myopathies with central nuclei. Wilmshurst JM, et al. Ann Neurol. 2010;68(5):717-26. doi:10.1002/ana.22119. PMID: 20839240.
  • Sambuughin N, Yau KS, Olivé M, Duff RM, Bayarsaikhan M, Lu S, Gonzalez-Mera L, Sivadorai P, Nowak KJ, Ravenscroft G, Mastaglia FL, North KN, Ilkovski B, Kremer H, Lammens M, van Engelen BG, Fabian V, Lamont P, Davis MR, Laing NG, Goldfarb LG. Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores. Am J Hum Genet. 2010;87(6):842-7. doi:10.1016/j.ajhg.2010.10.020. Epub 2010 Nov 25. PMID: 21109227.
  • Congenital myopathies: an update. Nance JR, et al. Curr Neurol Neurosci Rep. 2012;12(2):165-74. doi:10.1007/s11910-012-0255-x. PMID: 22392505.
  • Majczenko K, Davidson AE, Camelo-Piragua S, Agrawal PB, Manfready RA, Li X, Joshi S, Xu J, Peng W, Beggs AH, Li JZ, Burmeister M, Dowling JJ. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet. 2012;91(2):365-71. doi:10.1016/j.ajhg.2012.06.012. Epub 2012 Jul 19. PMID: 22818856.
  • Tajsharghi H, Oldfors A. Myosinopathies: pathology and mechanisms. Acta Neuropathol. 2013;125(1):3-18. doi:10.1007/s00401-012-1024-2. Epub 2012 Aug 05. PMID: 22918376.
  • Fardeau M, Tome F. Congenital Myopathies. In: Engel A, Franzini-Armstrong C, eds. Myology. New York, NY: McGraw-Hill, 1994: 1500-1505.
  • North K, Ryan MM. Nemaline Myopathy. 2002 Jun 19 [Updated 2012 Mar 15]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1288/
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1259
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1288
Clinical utility: Help
Establish or confirm diagnosis
View citations (29)
  • Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Pelin K, et al. Proc Natl Acad Sci U S A. 1999;96(5):2305-10. doi:10.1073/pnas.96.5.2305. PMID: 10051637.
  • MTM1 mutations in X-linked myotubular myopathy. Laporte J, et al. Hum Mutat. 2000;15(5):393-409. doi:10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R. PMID: 10790201.
  • Johnston JJ, Kelley RI, Crawford TO, Morton DH, Agarwala R, Koch T, Schäffer AA, Francomano CA, Biesecker LG. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet. 2000;67(4):814-21. doi:10.1086/303089. Epub 2000 Aug 21. PMID: 10952871.
  • Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. Kerst B, et al. Neuromuscul Disord. 2000;10(8):572-7. doi:10.1016/s0960-8966(00)00150-4. PMID: 11053684.
  • Nemaline myopathy: a clinical study of 143 cases. Ryan MM, et al. Ann Neurol. 2001;50(3):312-20. doi:10.1002/ana.1080. PMID: 11558787.
  • Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. Donner K, et al. Neuromuscul Disord. 2002;12(2):151-8. doi:10.1016/s0960-8966(01)00252-8. PMID: 11738357.
  • Characterization of mutations in fifty North American patients with X-linked myotubular myopathy. Herman GE, et al. Hum Mutat. 2002;19(2):114-21. doi:10.1002/humu.10033. PMID: 11793470.
  • Congenital myopathies and related disorders. Taratuto AL, et al. Curr Opin Neurol. 2002;15(5):553-61. doi:10.1097/00019052-200210000-00006. PMID: 12351999.
  • Genotype-phenotype correlations in X-linked myotubular myopathy. McEntagart M, et al. Neuromuscul Disord. 2002;12(10):939-46. doi:10.1016/s0960-8966(02)00153-0. PMID: 12467749.
  • X-linked myotubular and centronuclear myopathies. Pierson CR, et al. J Neuropathol Exp Neurol. 2005;64(7):555-64. doi:10.1097/01.jnen.0000171653.17213.2e. PMID: 16042307.
  • SEPN1: associated with congenital fiber-type disproportion and insulin resistance. Clarke NF, et al. Ann Neurol. 2006;59(3):546-52. doi:10.1002/ana.20761. PMID: 16365872.
  • Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet. 2007;80(1):162-7. doi:10.1086/510402. Epub 2006 Nov 14. PMID: 17160903.
  • Jungbluth H, Zhou H, Sewry CA, Robb S, Treves S, Bitoun M, Guicheney P, Buj-Bello A, Bönnemann C, Muntoni F. Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. Neuromuscul Disord. 2007;17(4):338-45. doi:10.1016/j.nmd.2007.01.016. Epub 2007 Mar 21. PMID: 17376685.
  • Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL, Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007;39(9):1134-9. doi:10.1038/ng2086. Epub 2007 Aug 05. PMID: 17676042.
  • Echaniz-Laguna A, Nicot AS, Carré S, Franques J, Tranchant C, Dondaine N, Biancalana V, Mandel JL, Laporte J. Subtle central and peripheral nervous system abnormalities in a family with centronuclear myopathy and a novel dynamin 2 gene mutation. Neuromuscul Disord. 2007;17(11-12):955-9. doi:10.1016/j.nmd.2007.06.467. Epub 2007 Sep 06. PMID: 17825552.
  • Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset. Bitoun M, et al. Ann Neurol. 2007;62(6):666-70. doi:10.1002/ana.21235. PMID: 17932957.
  • Compton AG, Albrecht DE, Seto JT, Cooper ST, Ilkovski B, Jones KJ, Challis D, Mowat D, Ranscht B, Bahlo M, Froehner SC, North KN. Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy. Am J Hum Genet. 2008;83(6):714-24. doi:10.1016/j.ajhg.2008.10.022. Epub 2008 Nov 20. PMID: 19026398.
  • Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1). Laing NG, et al. Hum Mutat. 2009;30(9):1267-77. doi:10.1002/humu.21059. PMID: 19562689.
  • DeChene ET, Kang PB, Beggs AH. Congenital Fiber-Type Disproportion – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2007 Jan 12 [updated 2013 Apr 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301436.
  • North KN, Ryan MM. Nemaline Myopathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2002 Jun 19 [updated 2015 Jun 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301465.
  • RYR1 mutations are a common cause of congenital myopathies with central nuclei. Wilmshurst JM, et al. Ann Neurol. 2010;68(5):717-26. doi:10.1002/ana.22119. PMID: 20839240.
  • Sambuughin N, Yau KS, Olivé M, Duff RM, Bayarsaikhan M, Lu S, Gonzalez-Mera L, Sivadorai P, Nowak KJ, Ravenscroft G, Mastaglia FL, North KN, Ilkovski B, Kremer H, Lammens M, van Engelen BG, Fabian V, Lamont P, Davis MR, Laing NG, Goldfarb LG. Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores. Am J Hum Genet. 2010;87(6):842-7. doi:10.1016/j.ajhg.2010.10.020. Epub 2010 Nov 25. PMID: 21109227.
  • Congenital myopathies: an update. Nance JR, et al. Curr Neurol Neurosci Rep. 2012;12(2):165-74. doi:10.1007/s11910-012-0255-x. PMID: 22392505.
  • Majczenko K, Davidson AE, Camelo-Piragua S, Agrawal PB, Manfready RA, Li X, Joshi S, Xu J, Peng W, Beggs AH, Li JZ, Burmeister M, Dowling JJ. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet. 2012;91(2):365-71. doi:10.1016/j.ajhg.2012.06.012. Epub 2012 Jul 19. PMID: 22818856.
  • Tajsharghi H, Oldfors A. Myosinopathies: pathology and mechanisms. Acta Neuropathol. 2013;125(1):3-18. doi:10.1007/s00401-012-1024-2. Epub 2012 Aug 05. PMID: 22918376.
  • Fardeau M, Tome F. Congenital Myopathies. In: Engel A, Franzini-Armstrong C, eds. Myology. New York, NY: McGraw-Hill, 1994: 1500-1505.
  • North K, Ryan MM. Nemaline Myopathy. 2002 Jun 19 [Updated 2012 Mar 15]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1288/
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1259
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1288

Target population: Help
The target population for this test is patients suspected of having a diagnosis of Congenital Myopathy.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
Variants are identified and evaluated using a custom collection of bioinformatic tools and comprehensively interpreted by our team of directors and genetic counselors.

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes.
Research:
Is research allowed on the sample after clinical testing is complete? Help
http://dnatesting.uchicago.edu/research-consent-form
Recommended fields not provided:
Technical Information
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
Analytical Sensitivity 99-100% Accuracy 100% Precision 100%
Assay limitations: Help
This assay covers the coding and immediate flanking regions of the included genes. Variants in the promoter region and in other non-coding regions will not be detected. Variants that occur within regions of high homology and/or repetitiveness may not be detected due to issues with alignment. The technical sensitivity of … View more
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP
VUS:
Software used to interpret novel variations Help
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations Help
The laboratory reports novel variations.
Recommended fields not provided:
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
Additional Information

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.