Invitae Multiminicore Disease Panel


Test description

The Invitae Multiminicore Disease Panel analyzes the two genes associated with multiminicore disease (MmD), a congenital myopathy that is typically characterized by axial and proximal muscle weakness and by findings of multiple minicores on muscle biopsy. These genes were curated based on current available evidence to provide a comprehensive test for the known genetic causes of MmD.

Given that MmD is a genetically heterogeneous disorder, identification of the underlying genetic cause can help predict patient outcome and inform recurrence risk.

Order test

Primary panel (2 genes)


RYR1: Deletion/duplication analysis is not offered for exons 48 or 49.
SEPN1: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.

Alternative tests to consider

For a broader analysis of genes associated with congenital myopathies, clinicians may consider the Invitae Congenital Fiber Type Disproportion Panel, the Invitae Congenital Myopathy Panel, or the Invitae Comprehensive Myopathy Panel. These broader panels can be ordered at no additional charge.

  • Multiminicore disease
  • Central core disease

MmD is a congenital myopathy that is characterized by muscle biopsy findings of minicores, which are small, focal muscle fiber lesions with sarcomeric disorganization and lack of oxidative activity. The classic form of MmD is associated with infantile or early-childhood onset hypotonia, delayed motor development, and slowly progressive axial and proximal muscle weakness. Spinal rigidity, progressive scoliosis, and respiratory involvement are common in classic MmD, and cardiac disease may develop secondary to respiratory issues. Affected individuals may remain ambulatory into adulthood despite significant scoliosis and respiratory issues. Atypical presentations of MmD also exist, including a form with distal weakness, joint hyperlaxity, and amyotrophy of the hands, a form with external ophthalmoplegia, and a severe neonatal form associated with congenital contractures.

The RYR1 gene is also associated with malignant hyperthermia susceptibility (MHS), a pharmacogenetic disorder characterized by susceptibility to uncontrolled skeletal muscle hypermetabolism after exposure to certain volatile anesthetics. Some individuals with RYR1-related MmD may have increased risk of MHS. SEPN1-related MmD is not known to be associated with MHS.

RYR1 and SEPN1 are the only genes known to be associated with MmD. Pathogenic variants in SEPN1 account for an estimated 30%–54% of cases. The proportion of cases of MmD caused by pathogenic variants in RYR1 is unknown.

MmD is typically inherited in an autosomal recessive pattern.

The prevalence of MmD is unknown, but it is thought to be a rare disorder. MmD has been identified in a diverse range of ethnicities.

The clinical presentation of MmD is variable. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help to 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
RYR1* NM_000540.2
SEPN1* NM_020451.2

RYR1: Deletion/duplication analysis is not offered for exons 48 or 49.
SEPN1: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.