Familial Hypercholesterolemia - Clinical Genetic Test - GTR

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Familial Hypercholesterolemia

Clinical Genetic Test

offered by

Clinical Biochemical Genetics Diagnostic Laboratory

GTR Test Accession: GTR000591888.1

CAP

INHERITED DISEASEMETABOLIC DISEASE

Registered in GTR: 2020-10-05

Last annual review date for the lab: 2024-10-10

At a Glance

Test purpose:

Diagnosis; Recurrence

Conditions (1):

Familial hypercholesterolemia

Genes (4):

APOB (2p24.1); LDLR (19p13.2); LDLRAP1 (1p36.11); PCSK9 (1p32.3)

Methods (1):

Molecular Genetics - Sequence analysis of select exons: Next-Generation (NGS)/Massively parallel sequencing (MPS)

Target population:

Not provided

Clinical validity:

Not provided

Clinical utility:

Not provided

Ordering Information

Offered by:

Clinical Biochemical Genetics Diagnostic Laboratory
View lab's website

Specimen Source:

Buccal swab
Peripheral (whole) blood
Saliva

Who can order:

Health Care Provider
Licensed Dentist
Licensed Physician
Nurse Practitioner

Lab contact:

Jingyu Huang, PhD, Lab Associate Director
jxh951@med.miami.edu
305-243-4856

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

Order a test:
For specimen requirements and shipping conditions, please check the information page of the desired test(s) located at http://medgen.med.miami.edu/bgdl/test-menu. All specimen tubes should be labeled with the patient’s name and date of birth.

Please fill out the Biochem Lab Requisition Online Form completely (http://medgen.med.miami.edu/bgdl/test-order-form). An incomplete form …

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Order URL

Informed consent required:

Decline to answer

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Test Order Code, Test strategy, Test development

Conditions

Total conditions: 1

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 4

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 1

Method Category

Test method

Instrument

Sequence analysis of select exons

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Illumina NextSeq 500

Clinical Information

Test purpose:

Diagnosis; Recurrence

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
BMGDL laboratory adopts American College of Medical Genetics Guidelines for the variant interpretation. Reference: Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of … View more

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes.

Recommended fields not provided:

Clinical validity, Clinical utility, Target population, Are family members with defined clinical status recruited to assess significance of VUS without charge?, Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report

Technical Information

Test Procedure:

Genomic DNA obtained from the submitted samples are enriched for targeted regions using a hybridization-based technique and sequenced using Illumina technology. Unless otherwise indicated, all targeted regions are sequenced with ≥20x depth. Reads are aligned to a reference sequence (GRCh37), and sequence changes are identified and interpreted in the context … View more

View citations (1)

Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E, . ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013;15(9):733-47. doi:10.1038/gim.2013.92. Epub 2013 Jul 25. PMID: 23887774.

Test Confirmation:

Positive test results are confirmed by using Sanger sequencing

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

Accuracy 99.99% Sensitivity 99.82% Specificity 99.99% Precision 99.72% Repeatability 99.99% Reproducibility 99.99%

Assay limitations:

• This test cannot detect inversions, or other structural variants. • Sensitivity to detect insertions and deletions larger than 15bp is reduced. There is no separate copy number variant analysis performed. Therefore, this test may not detect copy number variants (deletions or duplications). • Expansions and contractions within trinucleotide repeat … • This test cannot detect inversions, or other structural variants. • Sensitivity to detect insertions and deletions larger than 15bp is reduced. There is no separate copy number variant analysis performed. Therefore, this test may not detect copy number variants (deletions or duplications). • Expansions and contractions within trinucleotide repeat regions may not be detected. • No sequence changes in the promoter region and other non-coding regions will be detected by this assay. • The method does not reliably detect mosaic variants which may or may not be detected. • This test reflects the analysis of an extracted DNA sample. In rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome. • The presence of a variant in the apparent homozygous state may be indicative of a deletion on an allele and may, in actuality, represent hemizygosity for the variant. • This test may not determine if two different heterozygous variants are located on the same or on different chromosome copies. • The gene variant interpretation may change as new medical and scientific information becomes available. What is considered state of the art or state of knowledge today will not be the same in the future, sometimes even in the near future. Often, as subsequent studies are done, either within the same family or others reported in the literature, the clinical interpretation may need to be modified. • Results of this test should be interpreted in the context of the clinical presentation and in consultation with a clinical geneticist. • Some exons cannot be efficiently captured, and some genes cannot be accurately sequenced because of the presence of multiple copies in the genome. Therefore, a small fraction of sequence variants relevant to the patient's health will not be detected. • Normal findings do not rule out the diagnosis of any disorder since some genetic abnormalities may be undetectable with this assay. View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Formal PT program

PT Provider:
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

Recommended fields not provided:

Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Not provided

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View APOB variations in ClinVar

View LDLR variations in ClinVar

View PCSK9 variations in ClinVar

Practice guidelines:

Consumer resources:

MedlinePlusGenetics (GHR)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.