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Protein C Deficiency via the PROC 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
8493 PROC 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8493PROC81479 81479(x2) $890 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 backbone).

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

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Protein C deficiency is a condition that increases the risk of developing abnormal blood clots. Symptoms vary greatly but are strongly correlated to the levels of protein C activity. Patients with a mild form of the disease may form deep vein thrombosis (DVT) leading to a life threatening pulmonary embolism. Environmental factors including increased age, surgery, inactivity, pregnancy, smoking, and oral contraceptives have been shown to further enhance risks for DVT. Severe forms of the disease are congenital with infants developing life threatening purpura fulminans. These clots block normal blood flow leading to tissue necrosis (Goldenberg and Manco-Johnson 2008; Ohga et al. 2013). An estimated 1 in 500 individuals have mild and 1 in a million individuals have the severe form of protein C deficiency. Purified protein C, fresh frozen plasma, and other anticoagulation therapies such as warfarin have been used to mitigate clotting in patients with protein C deficiency (Price et al 2011; de Kort et al. 2011). In some cases therapy may be employed life-long. Genetic testing may aid in differential diagnosis between inherited and acquired forms of protein C deficiency as well as from protein S deficiency, antithrombin deficiency, and other hypercoagulability disorders.

Genetics

Protein C deficiency is inherited in an autosomal dominant manner with variable penetrance due to mutations in the PROC gene. Autosomal recessive and compound heterozygous individuals have the severe form of the disease. Causative mutations have been documented throughout the entire PROC gene with missense mutations affecting protein stability found in ~75% of cases (Gandrille and Aiach 1995; Rovida et al. 2007; D’Ursi et al 2007). Small insertions, deletions, and splicing mutations make up the majority of all other causative variants while large deletions are rarely found. Thrombophilia risk is also increased through mutations in the F5 (Factor V Leiden), F2 (Prothrombin 20210), and SERPINC1 genes (Caspers et al. 2012). Activated protein C functions as an anticoagulant by cleaving procoagulant factors V and VIII thereby preventing thrombin generation required for clotting.

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing by this method is capable of identifying >95% of causative mutations for protein C deficiency. In patients with a diagnosis of type I protein C deficiency, a PROC mutation was identified in ~85% of cases (Gandrille and Aiach 1995; Alhenc-Gelas et al. 2000).

Testing Strategy

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

Patients with protein C activity levels at <70% are ideal candidates. Individuals with type I deficiency in protein C have concordant decreases in both protein C levels and activity whereas type II deficiency displays decreases in protein C activity but normal protein levels. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PROC.

Gene

Official Gene Symbol OMIM ID
PROC 612283
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Alhenc-Gelas M, Gandrille S, Aubry ML, Aiach M. 2000. Thirty-three novel mutations in the protein C gene. French INSERM network on molecular abnormalities responsible for protein C and protein S. Thromb. Haemost. 83: 86–92. PubMed ID: 10669160
  • Caspers M, Pavlova A, Driesen J, Harbrecht U, Klamroth R, Kadar J, Fischer R, Kemkes-Matthes B, Oldenburg J. 2012. Deficiencies of antithrombin, protein C and protein S - practical experience in genetic analysis of a large patient cohort. Thromb. Haemost. 108: 247–257. PubMed ID: 22627591
  • de Kort EHM, Vrancken SLAG, Heijst AFJ van, Binkhorst M, Cuppen MPJM, Brons PPT. 2011. Long-term subcutaneous protein C replacement in neonatal severe protein C deficiency. Pediatrics 127: e1338–1342. PubMed ID: 21482600
  • D’Ursi P, Marino F, Caprera A, Milanesi L, Faioni EM, Rovida E. 2007. ProCMD: a database and 3D web resource for protein C mutants. BMC Bioinformatics 8 Suppl 1: S11. PubMed ID: 17430555
  • Gandrille S, Aiach M. 1995. Identification of mutations in 90 of 121 consecutive symptomatic French patients with a type I protein C deficiency. The French INSERM Network on Molecular Abnormalities Responsible for Protein C and Protein S deficiencies. Blood 86: 2598–2605. PubMed ID: 7670104
  • Goldenberg NA, Manco-Johnson MJ. 2008. Protein C deficiency. Haemophilia 14: 1214–1221. PubMed ID: 19141162
  • Ohga S, Kang D, Kinjo T, Ochiai M, Doi T, Ishimura M, Kayamori Y, Urata M, Yamamoto J, Suenobu S-I, Kanegane H, Ikenoue T, et al. 2013. Paediatric presentation and outcome of congenital protein C deficiency in Japan. Haemophilia 19: 378–384. PubMed ID: 23379934
  • Price VE, Ledingham DL, Krümpel A, Chan AK. 2011. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med 16: 318–322. PubMed ID: 21839696
  • Rovida E, Merati G, D’Ursi P, Zanardelli S, Marino F, Fontana G, Castaman G, Faioni EM. 2007. Identification and computationally-based structural interpretation of naturally occurring variants of human protein C. Hum. Mutat. 28: 345–355. PubMed ID: 17152060

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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