• Test code: 02401
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Familial Hypercholesterolemia Panel

Test description

This test provides a comprehensive analysis of the genes associated with familial hypercholesterolemia (FH).

Individuals with unexplained elevated cholesterol or early cardiovascular disease may benefit from the confirmation of an FH diagnosis through genetic testing to enable appropriate medical management and more targeted therapy. Early and appropriate medical intervention can reduce the risk of cardiovascular events. At-risk relatives could be identified and preventive therapy could be initiated. The Centers for Disease Control (CDC) Office of Public Health Genomics has categorized genetic testing for FH as a “Tier 1” classification, which indicates that there is evidence to support the use of this genetic test in medical practice.

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Primary panel (4 genes)
  • familial hypercholesterolemia (FH)

Familial hypercholesterolemia (FH) is characterized by an increase of low-density lipoprotein cholesterol (LDL-C) that can cause plaque to build up in the arteries (atherosclerotic plaque deposits) at an early age. This build-up of plaque can lead to the development of premature coronary artery disease (CAD). CAD leads to an increased risk for heart attack and stroke.

Some individuals with FH may have no symptoms and are only found to have elevated LDL-C levels through routine lipid testing. Individuals with FH may come to medical attention due to symptoms that are related to the development of cardiovascular disease. These symptoms can include chest pain, heart attack, stroke, and/or peripheral vascular disease. Some individuals with FH are found to have xanthomas (fatty skin growths) and/or corneal arci (cholesterol deposits in the eye).

Approximately 60%-80% of individuals with FH are expected to have a pathogenic variant identified in one of the genes on this panel. A negative genetic test result does not rule out the possibility that an individual may have FH.

Gene% of FH cases attributed
PCSK9Up to 3%

FH is inherited in both autosomal dominant and autosomal recessive patterns.

FH exhibits reduced penetrance, meaning not everyone who inherits a predisposition to develop FH will go on to manifest the disorder. However, the penetrance is high—estimated at 90% for individuals with pathogenic variants in LDLR and PCSK9.

Individuals with untreated FH and one pathogenic variant are 20 times more likely to develop coronary heart disease. Men have a 50% risk by age 50 years and women have a 30% risk by age 65 years. Individuals with untreated FH and two pathogenic variants are at risk of developing overt atherosclerosis before 20 years of age. Early or preventive intervention—medications to lower lipid levels and diet and lifestyle changes—can substantially reduce the risk of developing coronary heart disease in individuals with FH, bringing their risk for coronary heart disease closer to the general population’s.

The prevalence of autosomal dominant familial hypercholesterolemia is 1 in 200-500. It is higher in French Canadian, Christina Lebanese, and Ashkenazi Jewish populations. The prevalence of autosomal recessive familial hypercholesterolemia ranges from 1 in 160,000 to 1 in 1,000,000.

This test may be considered for individuals with:

  • a personal or family history of elevated levels of LDL-C (≥190 mg/dL in adults >20 years and ≥160 mg/dL in children <20 years)
  • a personal or family history of premature coronary artery disease or other forms of atherosclerosis, including stroke and/or peripheral vascular disease
  • physical findings characteristic of FH, such as xanthomas and corneal arci
  • a close blood relative who has FH

  1. Civeira F, et al. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004 Mar;173(1):55-68. PMID: 15177124
  2. De Castro-Orós, et al. The genetic basis of familial hypercholesterolemia: inheritance, linkage, and mutations. Appl Clin Genet. 2010 Aug 5;3:53-64. PMID: 23776352
  3. Goldberg AC, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun;5(3 Suppl):S1-8. PMID: 21600525
  4. Minhas R, et al. UK NICE Guideline on Identification and Management of FH (CG71) website. http://www.nice.org.uk/CG071. August 2008. Accessed August 14, 2015.
  5. Nordestgaard BG, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society 2013. Eur Heart J. 2013 Dec;34(45):3478-90a. PMID: 23956253
  6. Raal FJ, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011 Nov 15;124(20):2202-7. PMID: 21986285
  7. Robinson JG. Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm. 2013 Mar;19(2):139-49. PMID: 23461430
  8. Watts GF, et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol. 2014 Feb 15;171(3):309-25. PMID: 24418289
  9. Youngblom, E, Knowles, JW. Familial Hypercholesterolemia. 2014 Jan 02. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK174884/
  10. Youngblom, E, Knowles, JW. Familial Hypercholesterolemia. 2014 Jan 02. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 24404629

For links to published management guidelines, please refer to our Management guidelines page.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
APOB NM_000384.2
LDLR NM_000527.4
LDLRAP1 NM_015627.2
PCSK9 NM_174936.3