GeneSeq®: Cardio Early-onset Coronary Artery Disease/Familial Hypercholesterolemia Profile

CPT: 81401; 81406(x2); 81479
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Test Details

Test Includes

This test covers all coding nucleotides of 6 genes: ABCA1, APOA2, APOC3, LDLR, PCSK9, and PON2; plus at least two and typically 10 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 10 flanking nucleotides in the 5′ and 3′ UTR. This test also covers the region of APOB where all disease associated mutations have been found (within a 200-nucleotide region in exon 26 of APOB).

Use

Confirm a clinical diagnosis of coronary artery disease and identify presymptomatic family members, guiding prophylactic measures.

Limitations

This analysis does not rule out germline mosaicism, the presence of large chromosomal aberrations (including deletions, insertions, and rearrangements), mutations in regions or genes not included in this test, and possible inter/intragenic interactions between sequence variants. False-positive or false-negative results may occur for reasons that include genetic variants, blood transfusions, bone marrow transplantation, mislabeled specimens, or erroneous representation of family relationships.

Methodology

Mutation analysis is performed using the Agilent Sure Select XT® enrichment method and the Illumina® next-generation sequencing platform. Regions of the interest include all exons and splice junctions for each gene and limited regions for the following: SHOC2 (exon 2), APOB (556bp of exon 26), and AKAP9 (exon 18). Sequencing reads are aligned with the hg19 build of the human genome reference sequence. Analytical sensitivity is based on the depth of coverage across the regions of interest and is provided separately for each gene. Greater than 98% of target bases are synonymous variants not previously recorded at ≥20x coverage. Sanger sequencing is used to confirm mutation identity and analyze regions with low coverage. Variants are reported using numbering and nomenclature recommended by the Human Genome Variation Society (HGVS). Variants known to be benign and synonymous variants not previously recorded in our internal variant data bases are not reported.

Additional Information

Coronary artery disease (CAD) affects roughly 8% of Americans 20 years of age and older and is one of the leading causes of morbidity and mortality in the US. Genetic testing for the presence of germline mutations in the genes known to be associated with early-onset CAD and familial hypercholesterolemia (FH) may:

• Confirm a diagnosis of familial hypercholesterolemia

• Identify first-degree relatives of an index patient who has FH or early-onset coronary artery disease are at increased risk and may benefit from the initiation of preventative treatment

• Identify patients who carry mutations in lipid biosynthesis genes who may be at increased risk for CAD and may benefit from regular cardiac screening

• Facilitate appropriate genetic counseling

Specimen Requirements

Specimen

Whole blood

Volume

10 mL whole blood or 30 mL if ordering multiple tests

Container

Yellow-top (ACD) tube or lavender-top (EDTA) tube

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Frozen specimen; container broken or leaking; container not labeled or label not legible; improper anticoagulant

Clinical Information

Special Instructions

Test orders must include an attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. Please call customer service at 866-647-0735 before submitting specimens for family testing (ie, known mutations).

References

Gotto AM Jr. Targeting high-risk young patients for statin therapy. JAMA. 2004 Jul 21; 292(3): 377-378. 15265854
Leren TP. Cascade genetic screening for familial hypercholesterolemia. Clin Genet. 2004 Dec; 66(6):483-487. 15521974
Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics−2010 update: A report from the American Heart Association. Circulation. 2012 Feb 23; 121(7):e46-e215. 20019324
Oram JF. Tangier disease and ABCA1. Biochem Biophys Acta. 2000 Dec 15;1529(1-3):321-330. 11111099
Rodenburg J, Vissers MN, Wiegman A, et al. Statin treatment in children with familial hypercholesterolemia; the younger, the better. Circulation. 2007 Aug 7; 116(6):664-668. 17664376
Sanghera DK, Aston CE, Saha N, Kamboh MI. DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease. Am J Hum Genet. 1998 Jan; 62(1):36-44. 9443862
Takada D, Emi M, Ezura Y, et al. Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred. J Hum Genet. 2002; 47(12):656-664. 12522687
Varret M, Abifadel M, Rabès JP, Boileau C. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet. 2008 Jan; 73(1):1-13. 18028451
Willer CJ, Sanna S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008 Feb; 40(2):161-169. 18193043
Wilson P, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-1847. 9603539

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
451416 GeneSeq: Coronary Artery Disea 451331 Specimen Type: 31208-2
451416 GeneSeq: Coronary Artery Disea 451418 Results: 48003-8
451416 GeneSeq: Coronary Artery Disea 451404 Key Findings 53037-8
451416 GeneSeq: Coronary Artery Disea 451405 Additional Information 49549-9
451416 GeneSeq: Coronary Artery Disea 451406 Gene Information 51968-6
451416 GeneSeq: Coronary Artery Disea 451407 Tech Spec Results 51958-7
451416 GeneSeq: Coronary Artery Disea 451408 Seq Variants Detected 69548-6
451416 GeneSeq: Coronary Artery Disea 451409 Disclaimer N/A
451416 GeneSeq: Coronary Artery Disea 451411 Director Review: 48672-0
451416 GeneSeq: Coronary Artery Disea 451413 PDF 51969-4
451416 GeneSeq: Coronary Artery Disea 451419 GeneSeq: Coronary Artery Disea N/A

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