Venous thromboembolism laboratory testing (factor V Leiden andfactor II c.*97G>A), 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Abstract

Factor V Leiden and factor II c.*97G>A (formerly referred to asprothrombin 20210G>A) are the two most common genetic variants associated withvenous thromboembolism (VTE). Testing for these variants is one of the most commonreferrals in clinical genetics laboratories. While the methodologies for testingthese two variants are relatively straightforward, the clinical implementation canbe complicated with regard to test indications, risk assessment of occurrence andrecurrence of VTE, and related genetic counseling. This document provides anoverview of VTE, information about the variants and their influence on risk,considerations before initiating genetic testing, and the clinical and analyticalsensitivity and specificity of the tests. Key information that should be included inthe laboratory report is also provided. Disease-specific statements are intended toaugment the general American College of Medical Genetics and Genomics (ACMG)technical standards for clinical genetics laboratories. Individual laboratories areresponsible for meeting the Clinical Laboratory Improvement Amendments(CLIA)/College of American Pathologists (CAP) quality assurance standards withrespect to appropriate sample documentation, assay validation, general proficiencytesting, and quality control measures. This 2018 edition of the ACMG technicalstandard updates and supersedes the 2005 edition on this topic. It is designed to bea checklist for genetic testing professionals who are already familiar with thedisease and the methods of analysis.