Invitae Limb-Girdle Muscular Dystrophy Panel
Test description
The Invitae Limb-Girdle Muscular Dystrophy Panel analyzes genes associated with limb-girdle muscular dystrophy (LGMD), a heterogeneous group of conditions characterized by muscle weakness and wasting primarily affecting the limb-girdle musculature. These genes were curated based on currently available evidence to provide a comprehensive test for the genetic causes of LGMD. 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, help predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.
Genes tested
Primary panel
ANO5 CAPN3 CAV3 DAG1 DES DMD DNAJB6 DYSF FKRP FKTN GAA GMPPB GOSR2 HNRNPDL ISPD LAMA2 LMNA MYOT PLEC PNPLA2 POMGNT1 POMGNT2 POMK POMT1 POMT2 SGCA SGCB SGCD SGCG SMCHD1 TCAP TK2 TNPO3 TOR1AIP1 TRAPPC11 TRIM32 TTN
Add-on Preliminary-evidence Genes for Limb-Girdle Muscular Dystrophy
KBTBD13 LIMS2
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 (37 genes)
Customized gene selection (0 included, 0 excluded)
ANO5 CAPN3 CAV3 DAG1 DES DMD DNAJB6 DYSF FKRP FKTN GAA GMPPB GOSR2 HNRNPDL ISPD LAMA2 LMNA MYOT PLEC PNPLA2 POMGNT1 POMGNT2 POMK POMT1 POMT2 SGCA SGCB SGCD SGCG SMCHD1 TCAP TK2 TNPO3 TOR1AIP1 TRAPPC11 TRIM32 TTN
Add-on Preliminary-evidence Genes for Limb-Girdle Muscular Dystrophy (2 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
Alternative tests to consider
Clinical information
Disorders tested
Broad disorder tested:
- Limb-Girdle Muscular Dystrophy
Individual disorders tested:
- 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)
- Dystroglycanopathies
- muscular dystrophy-dystroglycanopathy type A1 (MDDGA1), type B1 (MDDGB1), type C1 (MDDGC1)
- muscular dystrophy-dystroglycanopathy type A12 (MDDGA12), type C12 (MDDGC12)
- 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 A7 (MDDGA7), type C7 (MDDGC7)
- muscular dystrophy-dystroglycanopathy type A8 (MDDGA8), type C8 (MDDGC8)
- muscular dystrophy-dystroglycanopathy type A9 (MDDGA9), type C9 (MDDGC9)
- Other Disorders
- Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD)
- facioscapulohumeral muscular dystrophy 2 (FSHD2)
- glycogen storage disease type II (GSDII), Pompe disease
- GOSR2-associated progressive myoclonic epilepsy
- LAMA2-related muscular dystrophy (LAMA2 MD)
- laminopathies
- 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
Limb-girdle muscular dystrophy 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 | ||
| CAPN3* | NM_000070.2 | ||
| CAV3 | NM_033337.2 | ||
| DAG1 | NM_004393.5 | ||
| DES | NM_001927.3 | ||
| DMD* | NM_004006.2 | ||
| DNAJB6 | NM_058246.3 | ||
| DYSF | NM_003494.3 | ||
| 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 | ||
| KBTBD13 | NM_001101362.2 | ||
| LAMA2 | NM_000426.3 | ||
| 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 | ||
| SGCA | NM_000023.2 | ||
| SGCB | NM_000232.4 | ||
| SGCD | NM_000337.5 | ||
| SGCG | NM_000231.2 | ||
| SMCHD1 | NM_015295.2 | ||
| TCAP | NM_003673.3 | ||
| TK2 | NM_004614.4 | ||
| 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).
