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  • Test code: 03291
  • Turnaround time:
    10–21 calendar days (14 days on average)
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    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
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  1. Test Catalog
  2. Invitae Comprehensive Muscular Dystrophy Panel

Invitae Comprehensive Muscular Dystrophy Panel

Test description

The Invitae Comprehensive Muscular Dystrophy Panel analyzes up to 56 genes that are associated with inherited muscular dystrophies. Muscular dystrophies are a heterogeneous group of neuromuscular disorders that are characterized by weakness and wasting due to muscle dysfunction. Age of onset, symptom severity, and histopathological findings are variable between different forms of muscular dystrophies. The genes in this panel were curated based on current available evidence to provide a comprehensive test for the genetic causes of inherited muscular dystrophy.

Given the clinical overlap between different types of muscular dystrophy, comprehensive testing allows for a more efficient evaluation of several conditions based on a single indication for testing. Identification of the molecular basis of disease can be useful in confirming a diagnosis, predicting disease course, and informing recurrence risk.

Genes tested

Primary panel

ANO5 B3GALNT2 B4GAT1 CAPN3 CAV3 CHKB COL12A1 COL6A1 COL6A2 COL6A3 DAG1 DES DMD DNAJB6 DPM1 DPM2 DPM3 DYSF EMD FHL1 FKRP FKTN GAA GMPPB ISPD ITGA7 LAMA2 LARGE1 LMNA MYOT PLEC PNPLA2 POMGNT1 POMGNT2 POMK POMT1 POMT2 RXYLT1 SGCA SGCB SGCD SGCG TCAP TNPO3 TOR1AIP1 TRAPPC11 TRIM32 TTN

Add-on Preliminary-evidence Genes for Muscular Dystrophy

HNRNPDL LIMS2 SUN1 SUN2 SYNE1 SYNE2 TMEM43

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. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

Add-on Facioscapulohumeral Muscular Dystrophy Type 2 (FSHD2) Gene

SMCHD1

Pathogenic variants in SMCHD1 account for approximately 5% of facioscapulohumeral muscular dystrophy. SMCHD1 variants should be interpreted in the context of D4Z4 hypomethylation and a permissive 4qA haplotype, which is not part of this assay. Depending on the clinical presentation of the individual and within the context of additional laboratory results, clinicians may wish to broaden analysis by including this gene, which can be added at no additional charge.

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Primary panel (48 genes)

ANO5 B3GALNT2 B4GAT1 CAPN3 CAV3 CHKB COL12A1 COL6A1 COL6A2 COL6A3 DAG1 DES DMD DNAJB6 DPM1 DPM2 DPM3 DYSF EMD FHL1 FKRP FKTN GAA GMPPB ISPD ITGA7 LAMA2 LARGE1 LMNA MYOT PLEC PNPLA2 POMGNT1 POMGNT2 POMK POMT1 POMT2 RXYLT1 SGCA SGCB SGCD SGCG TCAP TNPO3 TOR1AIP1 TRAPPC11 TRIM32 TTN

Panel details and technical assay limitations
Add-on Preliminary-evidence Genes for Muscular Dystrophy (7 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. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

HNRNPDL LIMS2 SUN1 SUN2 SYNE1 SYNE2 TMEM43

Panel details and technical assay limitations
Add-on Facioscapulohumeral Muscular Dystrophy Type 2 (FSHD2) Gene (1 gene)

Pathogenic variants in SMCHD1 account for approximately 5% of facioscapulohumeral muscular dystrophy. SMCHD1 variants should be interpreted in the context of D4Z4 hypomethylation and a permissive 4qA haplotype, which is not part of this assay. Depending on the clinical presentation of the individual and within the context of additional laboratory results, clinicians may wish to broaden analysis by including this gene, which can be added at no additional charge.

SMCHD1

Panel details and technical assay limitations

Alternative tests to consider

In some cases, muscular dystrophies may have overlapping features with myopathies. If a congenital myopathy is suspected, clinicians may consider the Invitae Congenital Myopathy Panel, or the Invitae Comprehensive Myopathy panel.

For a broader analysis of the genetics of hereditary neuromuscular disorders (muscular dystrophies, myopathies, and congenital myasthenic syndrome):

Clinical information

Muscular dystrophies are characterized by skeletal muscle dysfunction that leads to muscle weakness and wasting of varying severity. In specific forms, other muscles—including respiratory muscles, cardiac smooth muscles, and swallowing muscles—can also be affected. In rare variants, the disorder is associated with involvement of other organs or tissues, such as the brain, inner ear, eyes, or skin. Traditionally, the diagnosis of muscular dystrophies requires a comprehensive medical history and physical examination in addition to such investigations as a serum creatinine phosphokinase test, electromyography, and muscle biopsy. More recently, the majority of muscular dystrophies have been classified based on molecular genetic confirmation.

GeneInheritanceAssociated neuromuscular disorders and subtypes
Autosomal recessiveAutosomal dominantX-linked
ANO5 ✓ LGMD2L, Miyoshi muscular dystrophy-3
B3GALNT2 ✓ MDDGA11
B4GAT1 ✓ MDDGA13
CAPN3 ✓ LGMD2A
CAV3 ✓ ✓ LGMD1C, hypertrophic cardiomyopathy, hyperCKemia, distal myopathy
CHKB ✓ congenital muscular dystrophy, megaconial type
COL12A1 ✓ ✓ Bethlem myopathy, Ullrich congenital muscular dystrophy
COL6A1 ✓ ✓ Bethlem myopathy, Ullrich congenital muscular dystrophy
COL6A2 ✓ ✓ Bethlem myopathy, Ullrich congenital muscular dystrophy
COL6A3 ✓ ✓ Bethlem myopathy, Ullrich congenital muscular dystrophy
DAG1 ✓ MDDGA9, MDDGC9 (LGMD2P)
DES ✓ ✓ LGMD2R, myofibrillar myopathy-1, dilated cardiomyopathy
DMD ✓ Becker muscular dystrophy, Duchenne muscular dystrophy
DNAJB6 ✓ LGMD1E, distal myopathy
DPM1 ✓ CDG1E
DPM2 ✓ CDG1U
DPM3 ✓ CDG1O
DYSF ✓ LGMD2B, Miyoshi muscular dystrophy-1
EMD ✓ EDMD1
FHL1 ✓ EDMD6
FKRP ✓ MDDGA5, MDDGB5, MDDGC5 (LGMD2I), dilated cardiomyopathy
FKTN ✓ MDDGA4, MDDGB4, MDDGC4 (LGMD2M), dilated cardiomyopathy
GAA ✓ glycogen storage disease-2 (Pompe disease)
GMPPB ✓ MDDGA14, MDDGB14, MDDGC14 (LGMD2T)
HNRNPDL* ✓ LGMD1G
ISPD ✓ MDDGA7, MDDGC7 (LGMD2U)
ITGA7 ✓ congenital muscular dystrophy due to integrin alpha-7 deficiency
LAMA2 ✓ laminin alpha 2-deficient congenital muscular dystrophy/merosin-deficient congenital muscular dystrophy type 1A
LARGE1 (formerly known as LARGE) ✓ MDDGA6, MDDGB6
LIMS2* ✓ LGMD2W
LMNA ✓ ✓ Emery-Dreifuss muscular dystrophy, LGMD1B, congenital muscular dystrophy, dilated cardiomyopathy
MYOT ✓ LGMD1A, myofibrillar myopathy-3
PLEC ✓ LGMD2Q
PNPLA2 ✓ neutral lipid storage disease with myopathy (NLSDM)
POMGNT1 ✓ MDDGA3, MDDGB3, MDDGC3 (LGMD2O)
POMGNT2 ✓ MDDGA8
POMK ✓ MDDGA12, MDDGC12
POMT1 ✓ MDDGA1, MDDGB1, MDDGC1 (LGMD2K)
POMT2 ✓ MDDGA2, MDDGB2, MDDGC2 (LGMD2N)
RXYLT1 (formerly known as TMEM5) ✓ MDDGA10
SGCA ✓ LGMD2D
SGCB ✓ LGMD2E
SGCD ✓ ✓ LGMD2F, dilated cardiomyopathy
SGCG ✓ LGMD2C
SMCHD1 FSHD2 (digenic inheritance with D4Z4 hypomethylation and 4qA allele)
SUN1* ✓ Emery-Dreifuss muscular dystrophy
SUN2* ✓ Emery-Dreifuss muscular dystrophy
SYNE1* ✓ EDMD4
SYNE2* ✓ EDMD5
TCAP ✓ ✓ LGMD2G, dilated cardiomyopathy, hypertrophic cardiomyopathy
TMEM43* ✓ EDMD7
TNPO3 ✓ LGMD1F
TOR1AIP1 ✓ LGMD2Y
TRAPPC11 ✓ LGMD2S
TRIM32 ✓ LGMD2H, sarcotubular myopathy
TTN ✓ ✓ LGMD2J, tibial muscular dystrophy

*Preliminary-evidence gene

The clinical sensitivity of this test is dependent on the individual’s underlying genetic condition. Please see test specific pages for Invitae Type VI Collagenopathy, Invitae Emery-Dreifuss Muscular Dystrophy, Invitae Limb-Girdle Muscular Dystrophy, Invitae Dystroglycanopathy, and Invitae Congenital Muscular Dystrophy for disease-specific clinical sensitivity information. The Invitae Comprehensive Muscular Dystrophy Panel also includes other genes that have been identified as causes of muscular dystrophy, although the exact contribution of these genes to the overall detection rate is not known and is dependent on the clinical presentation of the individual. For some forms of muscular dystrophy, the underlying genetic cause remains unknown. As a result, a genetic diagnosis may not be achieved for some affected individuals, even upon testing all currently known causative genes.

Muscular dystrophies can be associated with different inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked. Some genes are associated with both autosomal dominant and autosomal recessive neuromuscular disorders. FSHD2 is associated with digenic inheritance.

For most forms of muscular dystrophy, penetrance is thought to be high. Depending on the causative gene, the age of symptom onset can be variable, ranging from childhood to late adulthood and making determination of penetrance difficult. FSHD2 has been reported to exhibit incomplete penetrance in 20% of individuals with a SMCHD1 mutation, hypomethylation of D4Z4 and a permissive 4qA allele.

Approximately 1 in 3,000–5,000 newborn males will be affected with Duchenne muscular dystrophy, making it the most common inherited muscle disease of childhood. Becker muscular dystrophy is much less common (approximately 1 in 20,000 male births). Of the limb-girdle muscular dystrophies, the recessive forms are more common than the dominant variants. Limb-girdle muscular dystrophy 2A seems to be more prevalent in southern Europe, whereas limb-girdle muscular dystrophy 2I is common in northern Europe, followed by limb-girdle muscular dystrophy 2B. Similarly, the frequencies of the different forms of congenital muscular dystrophy vary by region. Fukuyama muscular dystrophy is the most common CMD subtype in Japan due to a founder mutation in the FKTN gene. Laminin alpha-2 deficiency and type VI collagenopathies are the most common CMD subtypes in many countries with populations of European origin.

The clinical spectrum of muscular dystrophies is variable. Genetic testing may confirm a suspected diagnosis or rule out other disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform recurrence risk.

  1. Wang, CH, et al. Consensus statement on standard of care for congenital muscular dystrophies. J. Child Neurol. 2010; 25(12):1559-81. PMID: 21078917
  2. Mercuri, E, Muntoni, F. Muscular dystrophies. Lancet. 2013; 381(9869):845-60. PMID: 23465426
  3. Bönnemann, CG, et al. Diagnostic approach to the congenital muscular dystrophies. Neuromuscul. Disord. 2014; 24(4):289-311. PMID: 24581957
  4. Kang, PB, et al. Evidence-based guideline summary: Evaluation, diagnosis, and management of congenital muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology. 2015; 84(13):1369-78. PMID: 25825463
  5. Mah, JK, et al. A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies. Can J Neurol Sci. 2016; 43(1):163-77. PMID: 26786644
  6. Lemmers, RJ, et al. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat. Genet. 2012; 44(12):1370-4. PMID: 23143600

For management guidelines please refer to:

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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
ANO5 NM_213599.2
B3GALNT2 NM_152490.4
B4GAT1 NM_006876.2
CAPN3 NM_000070.2
CAV3 NM_033337.2
CHKB NM_005198.4
COL12A1 NM_004370.5
COL6A1 NM_001848.2
COL6A2 NM_001849.3
COL6A3 NM_004369.3
DAG1 NM_004393.5
DES NM_001927.3
DMD* NM_004006.2
DNAJB6 NM_058246.3
DPM1 NM_003859.1
DPM2 NM_003863.3
DPM3 NM_153741.1
DYSF NM_003494.3
EMD NM_000117.2
FHL1 NM_001449.4
FKRP NM_024301.4
FKTN* NM_001079802.1
GAA* NM_000152.3
GMPPB NM_013334.3
HNRNPDL NM_031372.3
ISPD NM_001101426.3
ITGA7 NM_002206.2
LAMA2 NM_000426.3
LARGE1 NM_004737.4
LIMS2 NM_001136037.2
LMNA NM_170707.3
MYOT NM_006790.2
PLEC NM_000445.4; NM_201378.3
PNPLA2 NM_020376.3
POMGNT1 NM_017739.3
POMGNT2 NM_032806.5
POMK NM_032237.4
POMT1 NM_007171.3
POMT2 NM_013382.5
RXYLT1 NM_014254.2
SGCA NM_000023.2
SGCB NM_000232.4
SGCD NM_000337.5
SGCG NM_000231.2
SMCHD1 NM_015295.2
SUN1 NM_001130965.2
SUN2 NM_015374.2
SYNE1 NM_033071.3
SYNE2 NM_182914.2
TCAP NM_003673.3
TMEM43 NM_024334.2
TNPO3 NM_012470.3
TOR1AIP1 NM_001267578.1
TRAPPC11 NM_021942.5
TRIM32 NM_012210.3
TTN* NM_001267550.2

DMD: Analysis guarantees del/dup detection at single-exon resolution.
FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T (also known as NM_001079802.1:c.648-1243G>T) and the ~3 kb retrotransposon insertion in the 3' UTR at position NM_001079802​.1:c.*4392_*4393.
GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
TTN: Deletion/duplication and sequencing analysis is not offered for exons 153-155 (NM_133378.4). 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).

Clinical resources
Invitae brochure Neurology gene list
Patient resources
Patient guide: Genetic testing simplified
Test information
Forms page Specimen requirements page

References

  1. Bönnemann, CG, et al. Diagnostic approach to the congenital muscular dystrophies. Neuromuscul. Disord. 2014; 24(4):289-311. PMID: 24581957
  2. Kang, PB, et al. Evidence-based guideline summary: Evaluation, diagnosis, and management of congenital muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology. 2015; 84(13):1369-78. PMID: 25825463
  3. Lemmers, RJ, et al. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat. Genet. 2012; 44(12):1370-4. PMID: 23143600
  4. Mah, JK, et al. A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies. Can J Neurol Sci. 2016; 43(1):163-77. PMID: 26786644
  5. Mercuri, E, Muntoni, F. Muscular dystrophies. Lancet. 2013; 381(9869):845-60. PMID: 23465426
  6. Wang, CH, et al. Consensus statement on standard of care for congenital muscular dystrophies. J. Child Neurol. 2010; 25(12):1559-81. PMID: 21078917

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