• Test code: 03366
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Distal Myopathy Panel

Test description

The Invitae Distal Myopathy Panel analyzes 18 genes that are associated with distal myopathies, a clinically and genetically heterogeneous group of disorders characterized by distal muscle weakness. Affected individuals may also have additional clinical findings, depending on the gene involved. The genes in this panel were curated based on current available evidence to provide a comprehensive test for the genetic causes of distal myopathies.

Given that distal myopathies are a heterogeneous group of disorders, identification of the underlying genetic cause can help predict outcome for the patient and inform recurrence risk.

Order test

Primary panel (18 genes)


Alternative tests to consider

For a broader analysis of genes associated with myopathies, clinicians may consider the Invitae Comprehensive Myopathy Panel. This broader panel can be ordered at no additional charge.

Distal myopathies are a clinically and genetically heterogeneous group of disorders associated with weakness that predominantly affects distal muscles of the toes, feet, legs, fingers, and hands. Depending on the causative gene, proximal muscle weakness, respiratory muscle involvement, and cardiomyopathy may also be observed. Creatine kinase (CK) levels in affected individuals vary from normal to significantly increased.

GeneDistal myopathy associated disorderInheritanceTypical age of onsetMost common presenting symptoms
Autosomal dominantAutosomal recessiveX-linked
ANO5 Miyoshi muscular dystrophy-3 early adulthood calf distal myopathy
BAG3 myofibrillar myopathy 6 childhood distal and/or proximal muscle weakness
CAV3 distal myopathy, Tateyama type adolescence to adulthood distal muscle weakness, atrophy of the muscles of the hands and feet
CRYAB myofibrillar myopathy 2 adulthood (AD), infantile (AR) slowly progressive distal and/or proximal muscle weakness
DES myofibrillar myopathy 1 variable (childhood to adulthood) variable— cardiomyopathy or distal and/or proximal muscle weakness
DNAJB6 DNAJB6-distal myopathy, myofibrillar myopathy variable (childhood to adulthood) distal and/or proximal muscle weakness
DYSF Miyoshi muscular dystrophy-1 adolescence to early adulthood distal leg muscle atrophy and weakness
FHL1 myofibrillar myopathy variable (childhood to adulthood) distal and/or proximal muscle weakness
FLNC distal myopathy-4, myofibrillar myopathy-5 adulthood distal and/or proximal muscle weakness
GNE GNE-related myopathy adolescence to early adulthood distal muscle weakness involving foot drop-induced gait difficulties
LDB3 myofibrillar myopathy-4 adulthood slowly progressive distal and/or proximal muscle weakness
MATR3 distal myopathy-2 adulthood distal lower limb muscle weakness
MYH7 Laing distal myopathy variable (infantile to late adulthood) initial weakness in ankle dorsiflexors and great toe
MYOT myofibrillar myopathy-3 adulthood distal weakness
SQSTM1 distal myopathy with rimmed vacuoles adulthood distal weakness
TIA1 Welander distal myopathy adulthood weakness of the index finger extensors
TTN tibial muscular dystrophy adulthood weakening and atrophy of the anterior compartment of the lower leg muscles, particularly the tibialis anterior muscle
VCP inclusion body myopathy with early-onset Paget disease and frontotemporal dementia adulthood distal and proximal muscle weakness

Distal myopathies are most commonly inherited in an autosomal dominant manner. Exceptions include the ANO5, DYSF, and GNE genes, which are associated with an autosomal recessive inheritance pattern. The CRYAB, DES, and TIA1 genes can be associated with either autosomal dominant or autosomal recessive distal myopathy. FHL1-associated distal myopathy is an X-linked disorder.

Distal myopathies are a diverse group of disorders whose penetrance varies according to the causative gene. Incomplete penetrance has been reported for certain genes, including DES, GNE, and MYH7. Some forms of distal myopathy do not present until late in adulthood, which makes determination of penetrance difficult.

Distal myopathies are a rare group of disorders, and the overall prevalence of these conditions is unknown.

The clinical spectrum of distal myopathies is broad. 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.

  1. Ruggieri, A, et al. Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal-onset DNAJB6 myopathy. Acta Neuropathol Commun. 2015; 3:44. PMID: 26205529
  2. Penttilä, S, et al. Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. Neurology. 2012; 78(12):897-903. PMID: 22402862
  3. Dimachkie, MM, Barohn, RJ. Distal myopathies. Neurol Clin. 2014; 32(3):817-42, x. PMID: 25037092
  4. Selcen, D, Engel, AG. Myofibrillar Myopathy. 2005 Jan 28. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1499/ PMID: 20301672
  5. Kimonis, V, et al. Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia. 2007 May 25. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301649
  6. Chauveau, C, et al. A rising titan: TTN review and mutation update. Hum. Mutat. 2014; 35(9):1046-59. PMID: 24980681
  7. Ahlberg, G, et al. Genetic linkage of Welander distal myopathy to chromosome 2p13. Ann. Neurol. 1999; 46(3):399-404. PMID: 10482271
  8. Müller, TJ, et al. Phenotype of matrin-3-related distal myopathy in 16 German patients. Ann. Neurol. 2014; 76(5):669-80. PMID: 25154462
  9. Lamont, P, Laing, NG. Laing Distal Myopathy. 2006 Oct 17. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301606
  10. O’Ferrall, EK, Sinnreich, M. GNE-Related Myopathy. 2004 Mar 26. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301439
  11. Duff, RM, et al. Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. Am. J. Hum. Genet. 2011; 88(6):729-40. PMID: 21620354
  12. Aoki, M. Dysferlinopathy. 2004 Feb 05. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301480

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. In addition, the analysis covers the select non-coding variants specifically defined in the table below. 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
BAG3 NM_004281.3
CAV3 NM_033337.2
CRYAB NM_001885.2
DES NM_001927.3
DNAJB6 NM_058246.3
DYSF NM_003494.3
FHL1 NM_001449.4
FLNC NM_001458.4
GNE NM_001128227.2
LDB3 NM_001080116.1; NM_001171610.1; NM_007078.2
MATR3 NM_199189.2
MYH7 NM_000257.3
MYOT NM_006790.2
SQSTM1 NM_003900.4
TIA1 NM_022173.2
TTN* NM_001267550.2
VCP NM_007126.3

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).