Congenital Myopathy Panel - Clinical Genetic Test - GTR

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Congenital Myopathy Panel

Clinical Genetic Test

offered by

Genetic Services Laboratory

View lab's test page

GTR Test Accession: GTR000506312.7

CAP

INHERITED DISEASEMUSCULOSKELETALNERVOUS SYSTEM ... View more

Last updated in GTR: 2021-01-19

Last annual review date for the lab: 2024-07-22

At a Glance

Test purpose:

Diagnosis; Monitoring; Mutation Confirmation; ...

Conditions (32):

Actin accumulation myopathy; Autosomal dominant centronuclear myopathy; Autosomal recessive limb-girdle muscular dystrophy type 2J more...

Genes (43):

ACTA1 (1q42.13); ACTN2 (1q43); BAG3 (10q26.11); BIN1 (2q14.3); CCDC78 (16p13.3) more...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...

Target population:

The target population for this test is patients suspected of …

Clinical validity:

NM is inherited in an autosomal dominant or autosomal recessive …

Clinical utility:

Establish or confirm diagnosis

Ordering Information

Offered by:

Genetic Services Laboratory
View lab's website
View lab's test page

Specimen Source:

Buccal swab
Cell culture
Fetal blood
Fibroblasts
Peripheral (whole) blood
Saliva
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant
Registered Nurse

CPT codes:

81443

**AMA CPT codes notice

Contact Policy:

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:

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:

Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings

Test additional service:

Custom Prenatal Testing
Custom mutation-specific/Carrier testing

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Test Order Code, Lab contact for this test, Test strategy

Conditions

Total conditions: 32

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 43

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

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:

Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Risk Assessment; Screening

Clinical validity:

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 … 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 risk information requires determination of the mode of inheritance, if possible, through pedigree analysis and a combination of clinical evaluation, molecular genetic testing, and muscle biopsy of the parents. Carrier testing for at-risk relatives in families with autosomal recessive NM is possible if the disease-causing mutations in the family are known. Prenatal molecular genetic testing is possible for pregnancies at increased risk for NM if the disease-causing mutation(s) in the family are known. BIN1 mutations appear to be relatively rare, accounting for approximately 25% of cases of CNM with apparent recessive inheritance but only a small percentage of all CNM cases combined. To date, only a small number of mutations have been described in the BIN1 gene, including several missense changes and nonsense mutations. The BIN1 gene codes for Bridging Integrator 1, also known as amphiphysin II, and has a muscle specific isoform. Amphiphysin II is regulated by phosphoinositides and is believed to be involved in membrane remodeling and T tubule organization. Majczenko et al, 2012, identified a heterozygous mutation in CCDC78 in a family with AD CNM. The CCDC78 gene encodes a protein that is important in skeletal muscle function. Compton et al, 2008 identified a homozygous frameshift mutation in the CNTN1 gene in affected individuals of a large consanguineous Egyptian family. The CNTN1 gene encodes for contactin-1, a neural adhesion molecular of the immunoglobulin superfamily. The majority of patients with autosomal dominant or later onset CNM, including DNM2-associated CNM, are ambulatory into adulthood. Intelligence is usually normal but at least one family with a DNM2 mutation has been reported to have mild cognitive impairment, as well as mild axonal peripheral nerve involvement. DNM2 mutations account for most, but not all, cases of CNM with autosomal dominant inheritance or later onset. NADH staining of patients with DNM2 mutations often reveals radial arrangement of sarcoplasmic strands, which is highly characteristic, but not diagnostic, of DNM2-associated CNM. Patients with X-linked myotubular myopathy (XLMTM) generally present with hypotonia, feeding difficulties, respiratory distress, and delayed motor milestones. Death in infancy is common in males with the classic form of this condition. Milder forms of XLMTM have been identified and are characterized by fewer respiratory complications and longer life expectancy than observed in the severe cases. Truncating and splice site MTM1 mutations are more likely to be associated with the severe neonatal form, whereas the milder phenotypes are often caused by missense mutations outside of the functional domains. Missense mutations may result in a mild or severe phenotype based on their position in the MTM1 gene. Approximately 80% of males with a diagnosis of myotubular myopathy by muscle biopsy will have a mutation in MTM1 identifiable by sequence analysis. About 7% of mutations in MTM1 are deletions. Kerst et al, 2000 identified a heterozygous missense mutation in the MYF6 gene in a boy with myopathy and an increase of muscle fibers with central nuclei. The MYF6 gene is a novel member of the human gene family of muscle determination factors. Heterozygous mutations in MYH7 have been associated with isolated hypertrophic/dilated cardiomyopathy, Laing distal myopathy and myosin storage myopathy. Inheritance is generally dominant, but recessive inheritance has been reported in at least one family with a more severe presentation that included cardiomyopathy. RYR1 is typically associated with autosomal recessive CNM, although a de novo autosomal dominant mutation in this gene has also been reported. CNM-associated mutations identified in RYR1 have included missense, frameshift, and intronic. Mutations in RYR1 have also been associated with malignant hyperthermia [OMIM#145600], central core disease [OMIM#117000] and multi-minicore disease [OMIM#255320]. The RYR1 gene, located at 19q13.2, encodes the skeletal muscle ryanodine receptor, which is the principal sarcoplasmic reticulum calcium release channel with a crucial role in excitation-contraction coupling. Clarke et al, 2006 identified a homozygous mutation in the SEPN1 gene in two sisters with congenital fiber type disproportion. Homozygous or compound heterozygous mutations in SEPN1 have also been seen in multi-minicore disease, rigid spine muscular dystrophy and desmin-related myopathy with Mallory body-like inclusions. Mutations in TTN have been described in patients with hereditary myopathy with early respiratory failure, tibial muscular dystrophy, and dilated cardiomyopathy type 1G. Titin is a muscle protein expressed in the cardiac and skeletal muscles and plays a key role in muscle assembly. 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, 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, 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://www.ncbi.nlm.nih.gov/books/NBK1288/
https://www.ncbi.nlm.nih.gov/books/NBK1259
https://www.ncbi.nlm.nih.gov/books/NBK1288

Clinical utility:

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, 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, 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://www.ncbi.nlm.nih.gov/books/NBK1288/
https://www.ncbi.nlm.nih.gov/books/NBK1259
https://www.ncbi.nlm.nih.gov/books/NBK1288

Target population:

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?
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?
Yes.

Research:

Is research allowed on the sample after clinical testing is complete?
http://dnatesting.uchicago.edu/research-consent-form

Recommended fields not provided:

Are family members with defined clinical status recruited to assess significance of VUS without charge?, Sample negative report, Sample positive report

Technical Information

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

Analytical Sensitivity 99-100% Accuracy 100% Precision 100%

Assay limitations:

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?
Yes

Method used for proficiency testing:
Formal PT program

PT Provider:
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

VUS:

Software used to interpret novel variations
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations
The laboratory reports novel variations.

Recommended fields not provided:

Test Confirmation, Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View ACTA1 variations in ClinVar

RefSeqGene

Coriell Institute for Medical Research

Practice guidelines:

EuroGenetest, 2012

Consumer resources:

Genetic Alliance

MalaCards

MedlinePlusGenetics (GHR)

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

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.