Hyperlipidemia Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: CA1101

Last modified: 12.19.2017

The Blueprint Genetics Hyperlipidemia Panel is an 11-gene test for genetic diagnostics of patients with clinical suspicion of disorder of lipoprotein metabolism, unspecified, familial hypercholesterolemia, lipoprotein deficiency, mixed hyperlipidaemia or other for of hyperlipidaemia.

Familial lipid disorders are inherited in an autosomal dominant and recessive manner. Genetic diagnostics can confirm or modify the clinical diagnosis in lipid disorders. It also enables effective identification of individuals carrying genetic defects that predispose to these diseases. Proband’s genetic diagnosis forms the basis for familial screening, which is especially useful for recognizing individuals whose disease has not yet manifested as abnormal lipid levels. Genetic diagnosis helps in adopting a healthy lifestyle at young age, allows early pharmacological treatment, and makes it possible to select patients with homozygous FH (HoFH) or equivalent disease (compound heterozygous or digenic heterozygous) for more aggressive treatment. Mutation detection may affect the therapy related compensation given for patients from government or insurance companies. Hyperlipidemia Panel includes the Hyperlipidemia- Core Panel.

About Hyperlipidemia

Familial lipid disorders such as hypercholesterolemia (FH) are inborn errors of metabolism that often produces high levels of blood cholesterol and predisposes to myocardial infarctions at an early age. In addition to lethal cardiovascular complications, inherited forms of hypercholesterolemia can also cause health problems related to the buildup of excess cholesterol in other tissues. If cholesterol accumulates in tendons, it causes characteristic growths called tendon xanthomas. These growths most often affect the Achilles tendons and tendons in the hands and fingers. Yellowish cholesterol deposits under the skin of the eyelids are known as xanthelasmata. Cholesterol can also accumulate at the edges of the clear, front surface of the eye (the cornea), leading to a gray-colored ring called an arcus cornealis. Familial hypercholesterolemia is usually an autosomal dominant/recessive disorder caused by mutations in LDLR, APOB, PCSK9 or LDLRAP1. Both APOB and PCSK9 related FH are clinically indistinguishable from heterozygous FH (HeFH) caused by LDLR mutations. Recessive forms of hypercholesterolemia are rare. Of these, FH associated with LDLRAP1 is clinically similar to HeFHs. On the contrary sitosterolemia, which is caused by ABCG5 and ABCG8 mutations, is a specific form of hyperlipidemia that manifests as hypercholesterolemia and high levels (30-100x normal) of plant sterols (phytosterols) in blood and other tissues. Clinical presentation of sitosterolemia includes xanthomas and coronary artery disease at an early age with conflict between the standard risk factor profile and the disease presentation. The familial lipoprotein lipase (LPL) deficiency (also called type 1 hyperlipoproteinemia) is an autosomal recessive condition distinct to other hyperlipidemias. It usually presents in childhood with very severe hypertriglyceridemia and episodic abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Hyperlipidemia Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ABCA1 Tangier disease, ABCA1 deficiency, HDL deficiency AD/AR 22 198
ABCG5 Sitosterolemia AR 10 36
ABCG8 Sitosterolemia AR 11 33
APOA1 Amyloidosis, systemic nonneuronopathic, Hypoalphalipoproteinemia AD/AR 26 69
APOB Hypobetalipoproteinemia, Hypercholesterolemia AD/AR 60 263
APOC3 Apolipoprotein C-III deficiency AD 6 8
APOE Sea-blue histiocyte disease, Dysbetalipoproteinemia, familial (Hyperlipoproteinemia), Lipoprotein glomerulopathy AD/AR 31 53
LDLR Hypercholesterolemia AD/AR 1691 2111
LDLRAP1 Hypercholesterolemia AR 9 19
LPL Lipoprotein lipase deficiency, Hyperlipoproteinemia, Combined hyperlipidemia, familial AD/AR 41 203
PCSK9 Hypercholesterolemia AD 31 74

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Gene Genomic location HG19 HGVS RefSeq RS-number
LDLR Chr19:11200124 c.-101T>C NM_000527.4 rs747068848
LDLR Chr19:11200090 c.-135C>G NM_000527.4
LDLR Chr19:11200089 c.-136C>G/T NM_000527.4
LDLR Chr19:11200087 c.-138T>C NM_000527.4
LDLR Chr19:11200086 c.-139C>G NM_000527.4
LDLR Chr19:11200073 c.-152C>T NM_000527.4
LDLR Chr19:11200069 c.-155_-154delACinsTTCTGCAAACTCCT NM_000527.4
LDLR Chr19:11200069 c.-156C>T NM_000527.4
LDLR Chr19:11200038 c.-185_-183delCTT NM_000527.4
LDLR Chr19:11224179 c.1359-31_1359-23delGCGCTGATGinsCGGCT NM_000527.4

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist


This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.


This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)


The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a comprehensive Hyperlipidemia Panel that covers classical genes associated with disorder of lipoprotein metabolism, unspecified, familial hypercholesterolemia, family history of familial hypercholesterolemia, lipoprotein deficiency, mixed hyperlipidaemia and other hyperlipidaemia. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

Find more info in Support

Choose an analysis method

$ $ 1400
$ $ 1000
$ $ 1600
Total $
Order now

ICD & CPT codes

CPT codes

SEQ 81401
SEQ 81405
SEQ 81406
DEL/DUP 81479

ICD codes

Commonly used ICD-10 codes when ordering the Hyperlipidemia Panel

ICD-10 Disease
E78.01 Familial hypercholesterolemia
E78.2 Mixed hyperlipidaemia
E78.4 Other hyperlipidaemia
E78.6 Lipoprotein deficiency
E78.9 Disorder of lipoprotein metabolism, unspecified
Z83.42 Family history of familial hypercholesterolemia

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

Subscribe to our newsletter