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Familial Hypercholesterolemia via the PCSK9 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
PCSK9 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9889PCSK981479 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

Familial Hypercholesterolemia (FH) is characterized by elevated serum levels of total cholesterol. It is primarily recognized clinically by severely elevated levels of low density lipoprotein (LDL) cholesterol. Typically, high LDL is considered anything above 160 mg/dL in persons under 20 years of age, and anything above 190 mg/dL in adults over 20 years of age (Hopkins et al. 2011). Accumulation of LDL can cause early onset atherosclerosis and increases the risk of coronary heart disease (CHD) by approximately 20% (Hopkins et al. 2011; Austin et al. 2004). By age 50, approximately 45% of male and 20% of female FH patients suffer from coronary artery disease (Goldstein et al. 2001). Other symptoms of FH include fatty skin deposits called xanthomas, cholesterol deposits in the eyelids, and chest pains associated with coronary artery disease. FH is present from birth and is phenotypically heterogeneous. Patients with FH often respond well to drug treatment, i.e. statins, and to lifestyle changes, including increased exercise and diets low in saturated fats, making early risk assessment and diagnosis very beneficial.


Familial Hypercholesterolemia is associated with heterozygous or homozygous mutations in one of three known genes: LDLR, APOB, and PCSK9. In general, heterozygous mutations in any one of these genes can result in a 2-3 fold increase in plasma LDL and a dramatically increased risk of heart disease compared to unaffected individuals. Homozygous or compound heterozygous patients are rare and generally have a much more severe phenotype with an early onset. The prevalence of heterozygous FH is around 1:500 in the U.S. White population and is similar for most European populations (Goldstein et al. 1973; Vuorio et al. 1997; Slack, J. 1979; Kalina et al. 2001; Austin et al. 2004). FH is particularly common among populations of African ancestry which have a reported prevalence as high as 1/67 (Austin et al. 2004). Most cases of FH are attributed to loss-of-function mutations in LDLR (van Aalst-Cohen et al. 2006) which encodes the LDL receptor. A small fraction of FH cases, <5%, are attributed to gain-of-function mutations in the PCSK9 gene (Abifadel et al. 2003; Hopkins et al. 2011). PCSK9 encodes the NARC-1 (neural apoptosis regulated convertase) protein which contributes to cholesterol homeostasis through degradation of LDLR (Abifadel et al. 2003). Gain-of-function variants in PCSK9 result in increased degradation of LDLR which increases serum LDL levels. Pathogenic variants have been reported throughout the PCSK9 gene and comprise primarily missense variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic gain-of-functions variants in the PCSK9 gene are found in < 5% of FH cases (Hopkins et al. 2011).

Few large deletions or duplications in the PCSK9 gene have been reported in cases of FH and they are a rare cause of FH.

Testing Strategy

This test provides full coverage of all coding exons of the PCSK9 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 the one or more of the following: very high levels of LDL cholesterol, low levels of LDLR, strong family history of cardiovascular disease, xanthomas, or fatty liver.


Official Gene Symbol OMIM ID
PCSK9 607786
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Hypercholesterolemia, Autosomal Dominant, 3 603776


  • Abifadel M, Varret M, Rabčs J-P, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, et al. 2003. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34: 154–156. PubMed ID: 12730697
  • Austin MA, Hutter CM, Zimmern RL, Humphries SE. 2004. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am. J. Epidemiol. 160: 407–420. PubMed ID: 15321837
  • Goldstein et al. 2001. In: The Metabolic and Molecular Basis of Inherited Disease - 8th edition (edited by C.R. Scriver et al.) New York: McGraw-Hill. 
  • Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, National Lipid Association Expert Panel on Familial Hypercholesterolemia. 2011. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 5: S9–17. PubMed ID: 21600530
  • Kalina A, Császár A, Czeizel AE, Romics L, Szabóki F, Szalai C, Reiber I, Németh A, Stephenson S, Williams RR. 2001. Frequency of the R3500Q mutation of the apolipoprotein B-100 gene in a sample screened clinically for familial hypercholesterolemia in Hungary. Atherosclerosis 154: 247–251. PubMed ID: 11137107
  • Slack, J. 1979. Inheritance of familial hypercholesterolemia. Atheroscler Rev 5:35-66.
  • van Aalst-Cohen, Jansen AC, Tanck MW, Defesche JC, Trip MD, Lansberg PJ, Stalenhoef AF, Kastelein JJ.. 2006. Diagnosing familial hypercholesterolaemia: the relevance of genetic testing. European Heart Journal 27: 2240–2246. PubMed ID: 16825289
  • Vuorio AF, Turtola H, Piilahti KM, Repo P, Kanninen T, Kontula K. 1997. Familial hypercholesterolemia in the Finnish north Karelia. A molecular, clinical, and genealogical study. Arterioscler. Thromb. Vasc. Biol. 17: 3127–3138. PubMed ID: 9409302


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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2) Select Additional Test Options

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