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Mitochondrial Complex V Deficiency via the ATPAF2 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
ATPAF2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8483ATPAF281479 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


  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Mitochondrial complex V deficiency is considered the rarest oxidative phosphorylation (OXPHOS) complex disorder, accounting for approximately one percent of all OXPHOS disease (Rodenburg 2011). Although patients with this disorder share a similar biochemical phenotype, with a significant decrease in the activity of mitochondrial complex V, the phenotypic disease spectrum can be broad (Hejzlarová et al. 2004; Jonckheere et al. 2012). Defects in complex V-associated nuclear genes often result in a severe, neonatal-onset mitochondrial encephalopathy and/or cardiomyopathy.

To date, only a single patient has been described with ATPAF2-associated mitochondrial complex V deficiency (De Meirleir et al. 2014; Meulemans et al. 2009). The affected individual presented as a neonate with degenerative encephalopathy, dysmorphic features, lactic acidosis, developmental delay, and seizures.


Mitochondrial complex V deficiency is caused by defects in the mitochondrial adenosine triphosphate (ATP) synthase, the fifth multi-subunit oxidative phosphorylation (OXPHOS) complex (Jonckheere et al. 2012; Hejzlarová et al. 2014). Although over 20 genes have been implicated in the assembly, structure, and function of the mitochondrial ATP synthase, variants in only six of these genes (ATP5A1, ATP5E, ATPAF2, TMEM70, MT-ATP6, and MT-ATP8) are currently associated with disease. Depending on the cellular localization of the affected gene, this disorder may have an autosomal recessive or maternal mode of inheritance. Causative variants in the nuclear genes (ATP5A1, ATP5E, ATPAF2, and TMEM70) are inherited in an autosomal recessive manner. In contrast, causative variants in the MT-ATP6 or MT-ATP8 genes, which are encoded by the mitochondrial genome, are inherited in a maternal manner.

The ATPAF2 gene (also referred to as Atp12p in the literature), encodes a chaperone protein thought to prevent aggregation of the F1 alpha subunit prior to its integration into the mitochondrial ATP synthase complex (Wang et al. 2001; Ackerman 2002). To date, only one pathogenic variant, a homozygous missense change, has been documented as a cause of ATPAF2-associated mitochondrial complex V deficiency (De Meirleir et al. 2004; Meulemans et al. 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

ATPAF2-associated mitochondrial complex V deficiency has been described in only one patient to date (De Meirleir et al. 2004). Although we cannot precisely estimate clinical sensitivity at this time, defects in ATPAF2 appear to be a rare cause of mitochondrial complex V deficiency. In contrast, defects in TMEM70 appear to be the most frequent cause of this disorder (Human Gene Mutation Database; http://www.hgmd.cf.ac.uk/ac/index.php).

Testing Strategy

This test provides full coverage of all coding exons of the ATPAF2 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).

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

ATPAF2 sequencing should be considered in patients with a family history of mitochondrial complex V deficiency, or patients who present with symptoms consistent with the disease. We will also sequence the ATPAF2 gene to determine carrier status.


Official Gene Symbol OMIM ID
ATPAF2 608918
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Mitochondrial Complex V Deficiency Panel (Nuclear Genes)


  • Ackerman S.H. 2002. Biochimica et Biophysica Acta. 1555:101-5. PubMed ID: 12206899
  • De Meirleir L. et al. 2004. Journal of Medical Genetics. 41:120-4. PubMed ID: 14757859
  • Hejzlarova K. et al. 2014. Physiological Research. 63:S57-1. PubMed ID: 24564666
  • Human Gene Mutation Database (Bio-base).
  • Jonckheere A.I. et al. 2012. Journal of Inherited Metabolic Disease. 35:211-25. PubMed ID: 21874297
  • Meulemans A. et al. 2010. Journal of Biological Chemistry. 285:4099-109. PubMed ID: 19933271
  • Rodenburg R.J. 2011. Journal of Inherited Metabolic Disease. 34:283-92. PubMed ID: 20440652
  • Wang Z.G. et al. 2001. Journal of Biological Chemistry. 276:30773-8. PubMed ID: 11410595


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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