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Hereditary Lymphedema via the GJC2 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
GJC2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8991GJC281479 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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


  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Primary lymphedema is a chronic condition of lymphatic drainage failure that arises from developmental or functional abnormalities of the lymphatic system. Lymphedema type 1C (OMIM 613480) presents most commonly with lower limb lymphedema. Onset ranges from birth to 40 years with most experiencing symptoms within the first or second decades (Ostergaard et al. J Med Genet 48:251-255, 2011). The severity of the disease varies from mild lower limb swelling to edema in all four limbs. More severe cases may involve skin infections and cellulitis (Ferrell et al. Am J Human Genet 86:943-948, 2010; Ostergaard et al. J Med Genet 48:251-255, 2011). Variants in the GJC2 gene are also associated with Pelizaeus-Merzbacher-like disease (PMLD, OMIM 608804). Patients with PMLD have reduced formation of myelin in the brain (Van der Knaap et al. Radiology 213:121-133, 1999) and present with nystagmus, hypotonia, motor delay, cerebellar ataxia, and spasticity (Uhlenberg et al. Am J Hum Genet 75:251-260, 2004).


Variants in the GJC2 gene associated with lymphedema are inherited in an autosomal dominant manner (Ferrell et al. Am J Human Genet 86:943-948, 2010), whereas variants in the GJC2 gene associated with PMLD are inherited in an autosomal recessive manner (Uhlenberg et al. Am J Hum Genet 75:251-260, 2004). The single coding exon of the GJC2 gene encodes a member of the connnexin family of proteins, connexin 47 (Cx47). Cx47 is expressed in lymphatic endothelial cells and in oligodendrocytes. Hexamers of connexin proteins form gap junctions, which are intercellular channels that connect adjacent cells and facilitate electrical and metabolic coupling. In patients with lymphedema, variants in GJC2 are predicted to alter gap junction function and disrupt lymphatic flow (Ferrell et al. Am J Human Genet 86:943-948, 2010) resulting in accumulation of lymph in interstitial space. Most causative GJC2 variants are missense variants though several nonsense variants and small and large insertions and deletions have been reported.

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is unknown.

Testing Strategy

This test provides full coverage of all coding exons of the GJC2 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

Candidates for this test are patients with clinical features of lymphedema or a family history of lymphedema. Additional candidates include patients with symptoms of hypomyelinating leukoencephalopathies, such as Pelizaeus-Merzbacher disease, who do not have variants in the PLP1 gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GJC2.


Official Gene Symbol OMIM ID
GJC2 608803
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Ferrell RE, Baty CJ, Kimak MA, Karlsson JM, Lawrence EC, Franke-Snyder M, Meriney SD, Feingold E, Finegold DN. 2010. GJC2 Missense Mutations Cause Human Lymphedema. The American Journal of Human Genetics 86: 943–948. PubMed ID: 20537300
  • Ferrell, R. E., et.al. (2008). "Candidate gene analysis in primary lymphedema." Lymphat Res Biol 6(2): 69-76. PubMed ID: 18564921
  • Ostergaard et al. Rapid identification of mutations in GJC2 in primary lymphoedema using whole exome sequencing combined with linkage analysis with delineation of the phenotype. J Med Genet 48:251-255, 2011. PubMed ID: 21266381
  • Uhlenberg B, Schuelke M, Rüschendorf F, Ruf N, Kaindl AM, Henneke M, Thiele H, Stoltenburg-Didinger G, Aksu F, Topalo\uglu H. 2004. Mutations in the Gene Encoding Gap Junction Protein α12 (Connexin 46.6) Cause Pelizaeus-Merzbacher–Like Disease. The American Journal of Human Genetics 75: 251–260. PubMed ID: 15192806
  • van der Knaap MS, Breiter SN, Naidu S, Hart AA, Valk J. 1999. Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach. Radiology 213: 121–133. PubMed ID: 10540652


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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View Ordering Instructions

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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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