Columbia Preventive Genomic Screen

Test Information

A number of genes in the human genome confer very high risk of preventable diseases when mutated. It has been estimated that about 1% of the adult population is predisposed to a serious hereditary condition that may be preventable or ameliorated through early diagnosis (PMID: 26540154). Appropriate genomic information can help individuals and their health care providers proactively make important health management decisions. The Columbia Preventive Genomic Screen uses exome sequencing (ES) technology to screen for genetic variants relevant to health in adults who are looking for insight and information about their genetic make-up.

Please note that the Precision Genomics Laboratory will only accept test requests after the patient has received genetic counseling from a health care provider for such a test. An informed consent form, signed by the patient (or by his/her authorized representative), as well as by the person obtaining consent should be submitted with each specimen.

Variant Information

We report variants in the following categories: 

  • Variants causing Treatable/Preventable Conditions (diseases which are clinically actionable): We follow the guidelines of the American College of Medical Genetics and Genomics for reporting of secondary findings in clinical exome and genome sequencing. Please consult the latest version of these guidelines for an up-to-date list of genes and conditions reported in this category.  
  • Variants causing Monogenic Mendelian Disease (single gene heritable disorders): These variants may be associated with dominant, recessive or X- linked disorders. We only report variants that are classified as Pathogenic/Likely Pathogenic following the American College of  Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines for the interpretation of sequence variants (PMID# 25741868). List of genes in this category can be found here.
  • Variants indicating Carrier Status for known Recessive Diseases: We only report variants that are classified as Pathogenic/ Likely Pathogenic following the ACMG- AMP guidelines. If the accompanying medical history OR family history is suggestive of the presence of a recessive condition in the family, then variants classified as “Variant of Uncertain Clinical Significance” may also be reported. List of genes in this category can be found here.
  • Risk Alleles: We report the following risk alleles: F5 (rs6025), SERPINC1 (rs121909551), F2(rs1799963), APOE (rs429358), APC (rs1801155) and HFE (rs1800562; homozygous only).
  • Pharmacogenomic Screening: We report the following variants: CYP2C19 (rs4244285, rs4986893, rs12248560), CYP2C9 (rs1799853, rs1057910), VKORC1 (rs9923231) and SLCO1B1 (rs4149056).

Options

Patients have the option of opting in/out to having their results automatically transmitted to the in the NYPH and Columbia University electronic medical record system.

Test Methods and Performance

A number of genes in the human genome confer very high risk of preventable diseases when mutated.  The Columbia Preventive Genomic Screen (CPGS) is a clinical exome sequencing based assay for screening genetic variants relevant to health in adults. For the CPGS test, the exome is sequenced to achieve an average minimum depth of 100X. On average >98% of target region is covered at ≥10X. Percentage of unique mapped reads is >70% and specificity on target is >50%. Analysis for this test is performed via the in-house Analysis Tool for Annotated Variants (ATAV) including variant filtering and prioritization.

Limitations and Risks

Limitations: ES is not able to detect mutations in the 99% of the DNA that is not part of the exome, including parts of the DNA that help regulate gene function. Coverage might vary by gene. Variation calling performance may vary by DNA sequence context. ES is not currently validated to detect large-scale alterations, such as microdeletions or microduplications (another genetic test called microarray is available for this purpose). ES may not be able to detect genetic disorders that are caused by expansion of repetitive regions of the genome, such as Huntington disease or some spinocerebellar ataxias. If one of these conditions is suspected, please order the appropriate test. Finding a disease-causing mutation may not result in a treatment, cure, or a prognosis. The test report is generated based on current medical knowledge. A mutation that is not known to be the cause of a genetic condition today may be shown to be disease causing in the future. Re-analysis and an updated report can be requested (for a fee).

Risks include possible discrimination based on genetic information: The Genetic Information Non- discrimination Act (GINA) is a federal law that prevents insurance companies and employers from using genetic information to deny health insurance coverage or for employment-related decisions. However, the law does not prevent companies that provide life insurance, disability insurance or long-term care insurance from using genetic information. In addition, ES may identify genetic changes that may require additional testing to be completely evaluated. This could result in anxiety, uncertainty, and additional expenses. ES may identify serious, untreatable genetic conditions. It can result in unexpected psychological trauma, both for the individual or his/her family.

Turnaround Time

Test results are reported to the referring physician within 2 months from the receipt of the specimen.

Specimen Requirements

  • *Blood: one 4ml or 10 ml EDTA (lavender top) tube
  • DNA specimens obtained from other CLIA certified laboratories
  • All specimens should carry two independent identifiers and be shipped at room temperature

*Preferred sample

Forms

Please contact us for additional information (including costs)

Email: pglsupport@cumc.columbia.edu

Telephone: (212) 305-5631