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Non-Syndromic Monogenic Obesity Panel

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
KSR2 81479,81479
LEP 81479,81479
LEPR 81406,81479
MC4R 81403,81479
NR0B2 81479,81479
NTRK2 81479,81479
PCSK1 81479,81479
POMC 81479,81479
SH2B1 81479,81479
SIM1 81479,81479
UCP3 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
15183Genes x (11)81479 81403(x1), 81406(x1), 81479(x20) $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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


  • Marissa Cloutier, PhD

Clinical Features and Genetics

Clinical Features

Obesity is defined as an increase in fat mass that is sufficient to adversely affect health and reduce longevity (Fontaine et al. 2003. PubMed ID: 12517229). Clinically, adults with a body-mass index (BMI) greater than 30 kg/m2 are considered obese. BMI is a multifactorial trait that is usually influenced by multiple genes (Gusev et al. 2014. PubMed ID: 25439723), as well as environmental and lifestyle factors. However, in some cases obesity is inherited by a monogenetic mechanism due to pathogenic variants in a single gene.

The non-syndromic form of monogenic obesity is a group of single gene disorders with obesity as an isolated or predominant feature. The obesity phenotype in these patients is typically severe and early-onset. Infants experience rapid weight gain in the first year of life and reach a BMI > 3 standard deviations above the mean. Associated features include hyperphagia, increased linear growth, delayed puberty, preserved reproductive function, hypocortisolemia and hyperinsulinemia (Albuquerque et al. 2015. PubMed ID: 25749980; Pigeyre et al. 2016. PubMed ID: 27154742)


The largest genetic contributors to non-syndromic obesity include genes expressed in the hypothalamus that control energy balance via the leptin-melanocortin signaling pathway (LEP, LEPR, MC4R, POMC, PCSK1, SH2B1, and SIM1). MC4R deficiency is the most prevalent of these disorders, affecting up to 1 in 2,000 individuals (Orphanet). Obesity due to pathogenic MC4R variants is inherited by a semidominant mechanism; the phenotype is severe and fully penetrant in homozygotes or compound heterozygotes, and milder with incomplete penetrance in heterozygotes. POMC and PCSK1 have similar inheritance properties. LEP and LEPR cause autosomal recessive obesity; SH2B1 and SIM1 cause obesity with autosomal dominant inheritance.

Additional genes mediate neuron differentiation and proliferation via tyrosine kinase signaling in the brain, apparently unrelated to the leptin pathway (NTRK2 and KSR2; Pigeyre et al. 2016. PubMed ID: 27154742). NTRK2 and KSR2-related obesity is autosomal dominant.

Finally, UCP3 and NR0B2 are involved in energy utilization in peripheral tissues such as skeletal muscle and liver (Millet et al. 1997. PubMed ID: 9389729; Lu et al. 2000. PubMed ID: 11030331). Pathogenic variants in these genes may cause obesity with autosomal dominant or recessive inheritance.

The genes included on this panel account for all known causes of monogenic non-syndromic obesity due to pathogenic sequence alterations. Pathogenic variants include missense and nonsense changes as well as small and large insertions/deletions (Human Gene Mutation Database). In some cases multifactorial inheritance has been proposed, however, at this time the number of cases is too small to clearly define these variants (Pigeyre et al. 2016. PubMed ID: 27154742).

Clinical Sensitivity - Sequencing with CNV PG-Select

It is difficult to estimate the clinical sensitivity of this test given the significant contribution of environment to obesity. For the MC4R gene alone, the prevalence of pathogenic variants is predicted to be 0.5 - 1% in obese adults and up to 6% in severely obese children (Farooqi and O'Rahilly. 2005. PubMed ID: 15660521; Farooqi et al. 2003. PubMed ID: 12646665). This range in prevalence demonstrates that sensitivity is strongly influenced by the severity and onset of symptoms.

The analytical sensitivity of this test is expected to be high since this Next-Generation sequencing test is designed to detect nearly all clinically relevant sequence and copy number variants in genes that cause monogenic obesity.

Testing Strategy

Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads.

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with non-syndromic obesity.


Official Gene Symbol OMIM ID
KSR2 610737
LEP 164160
LEPR 601007
MC4R 155541
NR0B2 604630
NTRK2 600456
PCSK1 162150
POMC 176830
SH2B1 608937
SIM1 603128
UCP3 602044
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test



  • Albuquerque et al. 2015. PubMed ID: 25749980
  • Farooqi and O'Rahilly. 2005. PubMed ID: 15660521
  • Farooqi et al. 2003. PubMed ID: 12646665
  • Fontaine et al. 2003. PubMed ID: 12517229
  • Gusev et al. 2014. PubMed ID: 25439723
  • Lu et al. 2000. PubMed ID: 11030331
  • Millet et al. 1997. PubMed ID: 9389729
  • Pigeyre et al. 2016. PubMed ID: 27154742


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

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View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

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