Invitae Comprehensive Muscular Dystrophy Panel
Test description
The Invitae Comprehensive Muscular Dystrophy Panel analyzes genes that are associated with inherited muscular dystrophies, a heterogeneous group of neuromuscular conditions that are characterized by weakness and wasting due to muscle dysfunction. The genetic heterogeneity associated with these conditions can make it difficult to use phenotype as the sole criterion to select a definitive cause. These genes were curated based on the available evidence to date in order to provide analysis for inherited muscular dystrophies. Given the clinical overlap of inherited muscular dystrophies, broad panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication. Some genes in this test may also be associated with additional unrelated disorders, which are not included in the list of disorders tested. Genetic testing of these genes may help confirm a clinical diagnosis, predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.
This assay does not currently test for facioscapulohumeral muscular dystrophy type 1 (FSHD1), oculopharyngeal muscular dystrophy (OPMD), or myotonic dystrophy types 1 and 2. Additional testing for these conditions should be considered, if not yet performed and clinically appropriate.
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 GOSR2 HNRNPDL ISPD ITGA7 LAMA2 LARGE1 LMNA MYOT PLEC PNPLA2 POMGNT1 POMGNT2 POMK POMT1 POMT2 RXYLT1 SGCA SGCB SGCD SGCG SMCHD1 TCAP TK2 TNPO3 TOR1AIP1 TRAPPC11 TRIM32 TTN
Add-on Preliminary-evidence Genes for Muscular Dystrophy
KBTBD13 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.
Order test
Primary panel (52 genes)
Customized gene selection (0 included, 0 excluded)
ANO5 B3GALNT2 B4GAT1 CAPN3 CAV3 CHKB COL12A1 COL6A1 COL6A2 COL6A3 DAG1 DES DMD DNAJB6 DPM1 DPM2 DPM3 DYSF EMD FHL1 FKRP FKTN GAA GMPPB GOSR2 HNRNPDL ISPD ITGA7 LAMA2 LARGE1 LMNA MYOT PLEC PNPLA2 POMGNT1 POMGNT2 POMK POMT1 POMT2 RXYLT1 SGCA SGCB SGCD SGCG SMCHD1 TCAP TK2 TNPO3 TOR1AIP1 TRAPPC11 TRIM32 TTN
Add-on Preliminary-evidence Genes for Muscular Dystrophy (7 genes)
Customized gene selection (0 included, 0 excluded)
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.
KBTBD13 LIMS2 SUN1 SUN2 SYNE1 SYNE2 TMEM43
Clinical information
Disorders tested
Broad disorders tested:
- Congenital Muscular Dystrophy
- Dystroglycanopathies
- Dystrophinopathies
- Emery-Dreifuss Muscular Dystrophy
- Limb-Girdle Muscular Dystrophy
- Type VI Collagenopathies
Individual disorders tested:
- Dystroglycanopathies
- muscular dystrophy-dystroglycanopathy type A1 (MDDGA1), type B1 (MDDGB1), type C1 (MDDGC1)
- muscular dystrophy-dystroglycanopathy type A10 (MDDGA10)
- muscular dystrophy-dystroglycanopathy type A11 (MDDGA11)
- muscular dystrophy-dystroglycanopathy type A12 (MDDGA12), type C12 (MDDGC12)
- muscular dystrophy-dystroglycanopathy type A13 (MDDGA13)
- muscular dystrophy-dystroglycanopathy type A14 (MDDGA14), type B14 (MDDGB14), type C14 (MDDGC14)
- muscular dystrophy-dystroglycanopathy type A2 (MDDGA2), type B2 (MDDGB2), type C2 (MDDGC2)
- muscular dystrophy-dystroglycanopathy type A3 (MDDGA3), type B3 (MDDGB3), type C3 (MDDGC3)
- muscular dystrophy-dystroglycanopathy type A4 (MDDGA4), Fukuyama congenital muscular dystrophy (FCMD), type B4 (MDDGB4), type C4 (MDDGC4)
- muscular dystrophy-dystroglycanopathy type A5 (MDDGA5), type B5 (MDDGB5), type C5 (MDDGC5)
- muscular dystrophy-dystroglycanopathy type A6 (MDDGA6), type B6 (MDDGB6)
- muscular dystrophy-dystroglycanopathy type A7 (MDDGA7), type C7 (MDDGC7)
- muscular dystrophy-dystroglycanopathy type A8 (MDDGA8, type C8 (MDDGC8)
- muscular dystrophy-dystroglycanopathy type A9 (MDDGA9)
- Dystrophinopathies
- Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD)
- Emery-Dreifuss Muscular Dystrophy (EDMD) Subtypes
- Emery-Dreifuss muscular dystrophy type 1 (EDMD1)
- Emery-Dreifuss muscular dystrophy type 2 (EDMD2), type 3 (EDMD3), laminopathies
- Emery-Dreifuss muscular dystrophy type 6 (EDMD6)
- Limb-Girdle Muscular Dystrophy (LGMD) Subtypes
- limb-girdle muscular dystrophy type 1A (LGMD1A)
- limb-girdle muscular dystrophy type 1C (LGMD1C), caveolinopathies
- limb-girdle muscular dystrophy type 1E (LGMD1E), type 1D (LGMD1D)
- limb-girdle muscular dystrophy type 1F (LGMD1F)
- limb-girdle muscular dystrophy type 1G (LGMDD3)
- limb-girdle muscular dystrophy type 2A (LGMD2A), type 4 (LGMDD4)
- limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi muscular dystrophy type 1 (MMD1), dysferlinopathies
- limb-girdle muscular dystrophy type 2C (LGMD2C)
- limb-girdle muscular dystrophy type 2D (LGMD2D)
- limb-girdle muscular dystrophy type 2E (LGMD2E)
- limb-girdle muscular dystrophy type 2F (LGMD2F)
- limb-girdle muscular dystrophy type 2G (LGMD2G)
- limb-girdle muscular dystrophy type 2H (LGMD2H)
- limb-girdle muscular dystrophy type 2J (LGMD2J), tibial muscular dystrophy (TMD)
- limb-girdle muscular dystrophy type 2L (LGMD2L), Miyoshi muscular dystrophy type 3 (MMD3)
- limb-girdle muscular dystrophy type 2Q (LGMD2Q)
- limb-girdle muscular dystrophy type 2R (LGMD2R)
- limb-girdle muscular dystrophy type 2S (LGMD2S)
- limb-girdle muscular dystrophy type 2Y (LGMD2Y)
- Type VI Collagenopathies
- Bethlem myopathy 1 (BTHLM1), Ullrich congenital muscular dystrophy 1 (UCMD1)
- Bethlem myopathy 2 (BTHLM2), Ullrich congenital muscular dystrophy 2 (UCMD2)
- Other Disorders
- congenital muscular dystrophy due to integrin alpha-7 deficiency
- congenital muscular dystrophy, megaconial type (MDCMC)
- DPM1-congenital disorder of glycosylation (CDG-Ie)
- DPM2-congenital disorder of glycosylation (CDG-Iu)
- DPM3-congenital disorder of glycosylation (CDG-Io)
- epidermolysis bullosa simplex with muscular dystrophy (EBSMDO)
- facioscapulohumeral muscular dystrophy 2 (FSHD2)
- glycogen storage disease type II (GSDII), Pompe disease
- GOSR2-associated progressive myoclonic epilepsy
- LAMA2-related muscular dystrophy (LAMA2 MD)
- mitochondrial DNA depletion syndrome 2 (MTDPS2)
- neutral lipid storage disease with myopathy (NLSDM)
Clinical description
To view the complete clinical description of this panel, click here.
Inheritance
Muscular dystrophies can be inherited in an autosomal dominant, autosomal recessive or X-linked pattern.
Assay
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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_021971.2 | ||
| GOSR2 | NM_004287.3 | ||
| HNRNPDL | NM_031372.3 | ||
| ISPD | NM_001101426.3 | ||
| ITGA7 | NM_002206.2 | ||
| KBTBD13 | NM_001101362.2 | ||
| 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 | ||
| TK2 | NM_004614.4 | ||
| TMEM43 | NM_024334.2 | ||
| TNPO3 | NM_012470.3 | ||
| TOR1AIP1 | NM_001267578.1 | ||
| TRAPPC11 | NM_021942.5 | ||
| TRIM32 | NM_012210.3 | ||
| TTN* | NM_001267550.2 |
CAPN3: Deletion/duplication analysis is not offered for exon 24.
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‚Äã.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: Exons 45-46, 147, 149, 164, 172-201 (NM_001267550.2) are excluded from analysis. TTN variants are included in the primary report based on functional effect and/or location. A complete list of variants of uncertain significance, likely benign and benign variants in TTN is available upon request. Variants are named relative to the NM_001267550.2 (meta) transcript. Variants in the coding sequence and intronic boundaries of the clinically relevant NM_133378.4 (N2A) and fetal isoforms are reported (PMID: 25589632, 29598826, 29691892, 31660661), with the exception of the PEVK tandem repeat region (172-198) (PMID: 28040389).
