Invitae Limb-Girdle Muscular Dystrophy Panel


Test description

The Invitae Limb-Girdle Muscular Dystrophy Panel analyzes up to 33 genes that are associated with limb-girdle muscular dystrophy (LGMD) — a heterogeneous group of disorders characterized by muscle weakness and wasting primarily affecting the limb-girdle musculature. These genes were curated based on current available evidence to provide a comprehensive test for the genetic causes of limb-girdle muscular dystrophy.

Given that limb-girdle muscular dystrophy is a heterogeneous group of disorders, identification of the underlying genetic cause can help predict outcome and inform recurrence risk.

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Primary panel (30 genes)


DMD: Analysis guarantees del/dup detection at single-exon resolution.
FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T as well as the 3 kb retrotransposon insertion in the 3' UTR at c.*4287_*4288ins3062.
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).

Add-on preliminary-evidence genes (3 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.


Alternative tests to consider

For a broader analysis of genes associated with muscular dystrophies, clinicians may consider the Invitae Comprehensive Muscular Dystrophy Panel.

Invitae Comprehensive Muscular Dystrophy Panel

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

Limb-girdle muscular dystrophies (LGMD) are a highly heterogeneous group of disorders that are characterized by progressive weakness and wasting of the limbs and pelvic and scapular muscles. Facial and distal muscles are typically spared, although distal muscle weakness can occur in the later stages of disease. Muscle biopsy typically shows signs of muscle necrosis and regeneration, with fibrosis and adipose tissue infiltration. Onset of symptoms is variable and typically ranges from childhood to adulthood. Some genes associated with the LGMD phenotype also have additional cardiopulmonary and extra-skeletal findings.

The spectrum of phenotypes that can occur in LGMD overlaps with a number of different neuromuscular conditions, including, in severe cases, Duchenne muscular dystrophy. Muscular dystrophy-dystroglycanopathies (MDDG) are a group of variable childhood onset disorders, the mildest form of which (MDDG type C) can present as a limb-girdle muscular dystrophy phenotype with or without intellectual disability.

GeneInheritanceAssociated neuromuscular disorders and subtypesTypical age of onsetProportion of LGMD cases
Autosomal recessiveAutosomal dominantX-linked
ANO5 LGMD2L, Miyoshi muscular dystrophy-3 adulthood 11%–25% of recessive forms of LGMD
CAPN3 LGMD2A childhood or adulthood 10%
CAV3 LGMD1C, hypertrophic cardiomyopathy, hyperCKemia, distal myopathy childhood 1%–2%
DAG1 MDDGA9, MDDGC9 (LGMD2P) childhood unknown
DES LGMD2R, myofibrillar myopathy-1, dilated cardiomyopathy adolescence or early adulthood unknown
DMD Becker muscular dystrophy, Duchenne muscular dystrophy childhood or adolescence n/a
DNAJB6 LGMD1E, distal myopathy mid-adulthood unknown
DYSF LGMD2B, Miyoshi muscular dystrophy-1 adolescence to early adulthood 5% of recessive LGMD
FKRP MDDGA5, MDDGB5, MDDGC5 (LGMD2I), dilated cardiomyopathy childhood to early adulthood unknown
FKTN MDDGA4, MDDGB4, MDDGC4 (LGMD2M), dilated cardiomyopathy childhood unknown
GAA Glycogen storage disease-2 (Pompe disease) variable n/a
GMPPB MDDGA14, MDDGB14, MDDGC14 (LGMD2T) infancy or childhood unknown
HNRNPDL* LGMD1G unknown unknown
ISPD MDDGA7, MDDGC7 (LGMD2U) infancy or childhood unknown
LIMS2* LGMD2W unknown unknown
LMNA Emery Dreifuss muscular dystrophy, LGMD1B, congenital muscular dystrophy, dilated cardiomyopathy variable unknown
MYOT LGMD1A, myofibrillar myopathy-3 childhood to adulthood unknown
PLEC LGMD2Q childhood unknown
PNPLA2 neutral lipid storage disease with myopathy early to late adulthood unknown
POMGNT1 MDDGA3, MDDGB3, MDDGC3 (LGMD2O) infancy to childhood unknown
POMK MDDGA12, MDDGC12 infancy to childhood unknown
POMT1 MDDGA1, MDDGB1, MDDGC1 (LGMD2K) infancy to childhood unknown
POMT2 MDDGA2, MDDGB2, MDDGC2 (LGMD2N) infancy to childhood unknown
SGCA LGMD2D childhood up to 38% of severe recessive forms of LGMD
SGCB LGMD2E childhood up to 12% of severe recessive forms of LGMD
SGCD LGMD2F, dilated cardiomyopathy childhood rare
SGCG LGMD2C childhood up to 17% of severe recessive forms of LGMD
TCAP LGMD2G, dilated cardiomyopathy, hypertrophic cardiomyopathy childhood to adolescence 3%
TNPO3 LGMD1F variable unknown
TOR1AIP1* Unknown unknown unknown
TRAPPC11 LGMD2S childhood unknown
TRIM32 LGMD2H, sarcotubular myopathy variable 3% of recessive forms of LGMD
TTN LGMD2J, tibial muscular dystrophy variable unknown

*Preliminary-evidence gene

Pathogenic variants in the sarcoglycan genes (SGCA, SGCB, SGCD, and SGCG) account for up to 68% of severe autosomal recessive forms of LGMD. ANO5 accounts for an additional 11%–25% of autosomal recessive LGMD while the CAPN3, DYSF, and TRIM32 genes each account for 10% or less. CAPN3-associated LGMD may be more common in populations with founder mutations, such as the Basque region in Spain. TTN-associated LGMD is only prevalent in the Finnish population due to a founder mutation. A TRIM32 founder mutation in the Hutterite population also exists. The CAV3, LMNA, and TCAP gene each account for 10% or less of LGMD overall.

The majority of LGMD subtypes are inherited in an autosomal recessive pattern. DNAJB6-, LMNA-, MYOT-, and TNPO3-associated disorders are autosomal dominant. DMD-associated disorders are X-linked. CAV3-associated LGMD can be inherited in either an autosomal dominant or recessive pattern. The DES, SGCD, TCAP, and TTN genes are all associated with autosomal recessive LGMD; however, these genes are also associated with other neuromuscular disorders with autosomal dominant inheritance.

For most forms of LGMD, penetrance is thought to be high. Depending on the causative gene, the age of onset of symptoms can be variable, ranging from childhood to late adulthood, which can make determination of penetrance difficult.

The prevalence of LGMD is estimated at 1 in 14,500–123,000. In Finland, the prevalence of ANO5-associated LGMD is estimated at 1 in 50,000.

The clinical presentation of limb-girdle muscular dystrophies can be variable. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform recurrence risk.

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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
HNRNPDL NM_031372.3
ISPD NM_001101426.3
LIMS2 NM_017980.4
LMNA NM_170707.3
MYOT NM_006790.2
PLEC NM_000445.4
PNPLA2 NM_020376.3
POMGNT1 NM_017739.3
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
TCAP NM_003673.3
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 as well as the 3 kb retrotransposon insertion in the 3' UTR at c.*4287_*4288ins3062.
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).