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Myopathy with Lactic Acidosis via the ISCU Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
ISCU 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8783ISCU81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Myopathy with lactic acidosis is a mitochondrial myopathy that presents with lifelong exercise intolerance, muscle fatigue, shortness of breath, and tachycardia with low levels of physical exertion (Mochel et al. 2008; Olsson et al. 2008; Kollberg et al. 2009). Muscle tenderness, cramping, and myoglobinuria may also be present. Patients show a low work and oxidative capacity in additional to deficiency in the succinate dehydrogenase and aconitase enzymes. Onset is typically noticed in childhood with episodes of rhabdomyolysis and myoglobinuria occurring during or after the second decade of life (Mochel and Haller 2016). Two brothers with early onset of a slowly progressive severe muscle weakness, severe exercise intolerance, and cardiomyopathy have also been reported (Kollberg et al. 2009; Saha et al. 2014).


Myopathy with lactic acidosis is inherited in an autosomal recessive manner due to pathogenic variants in ISCU, located on chromosome 12q24.1. The ISCU gene encodes the iron-sulfur cluster scaffold protein (ISCU). The common pathogenic Swedish c.418+382G>C intronic variant results in aberrant splicing and a premature stop codon in the penultimate exon (Mochel et al. 2008; Olsson et al. 2008). This change alters the C-terminus of the ISCU protein and results in decreased levels of ISCU protein which results in deficiency of multiple iron-sulfer containing mitochondrial enzymes including succinate dehydrogenase, aconitase, and respiratory chain complexes I and III (Mochel et al. 2008; Olsson et al. 2008). The only pathogenic variants reported to date are the c.418+382G>C intronic variant and a missense variant (c.149G>A). The c.149G>A variant in the compound heterozygous state with the c.418+382G>C was reported in two brothers with a more severe phenotype (Kollberg et al. 2009; Saha et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Many types of mitochondrial myopathies exist and may be difficult to distinguish from ISCU-related myopathy. The clinical sensitivity is uncertain; however, patients of Swedish descent with reduced activity of succinate dyhydrogenase and aconitase on muscle biopsy are most likely to harbor ISCU variants. Analytical sensitivity should be high as all reported pathogenic variants are detected by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the ISCU gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

This test also includes coverage of the common Swedish c.418+382G>C intronic variant.

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals of Swedish descent with exercise intolerance and suspected to have a mitochondrial myopathy. Reduced activity of succinate dehydrogenase and aconitase can also indicate an ISCU-related myopathy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ISCU.


Official Gene Symbol OMIM ID
ISCU 611911
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Myopathy With Lactic Acidosis, Hereditary AR 255125


  • Kollberg G. et al. 2009. Brain. 132: 2170-9. PubMed ID: 19567699
  • Mochel F. and Haller R.G. 2016. Myopathy with Deficiency of ISCU. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301757
  • Mochel F. et al. 2008. American Journal of Human Genetics. 82: 652-60. PubMed ID: 18304497
  • Olsson A. et al. 2008. Human Molecular Genetics. 17: 1666-72. PubMed ID: 18296749
  • Saha P.P. et al. 2014. The Journal of Biological Chemistry. 289: 10359-77. PubMed ID: 24573684


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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