Improving interpretation of genetic testing for hereditary hemorrhagic, thrombotic, and platelet disorders

Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):76-81. doi: 10.1182/hematology.2020000091.


The last 10 years have seen an explosion in the amount of data available through next-generation sequencing. These data are advancing quickly, and this pace makes it difficult for most practitioners to easily keep up with all of the new information. Complicating this understanding is sometimes conflicting information about variant pathogenicity or even about the role of some genes in the pathogenesis of disease. The more widespread clinical use of sequencing has expanded phenotypes, including the identification of mild phenotypes associated with previously serious disease, such as with some variants in RUNX1, MYH9, ITG2A, and others. Several organizations have taken up the task of cataloging and systematically evaluating genes and variants using a standardized approach and making the data publicly available so that others can benefit from their gene/variant curation. The efforts in testing for hereditary hemorrhagic, thrombotic, and platelet disorders have been led by the International Society on Thrombosis and Haemostasis Scientific Standardization Committee on Genomics in Thrombosis and Hemostasis, the American Society of Hematology, and the National Institutes of Health National Human Genome Research Institute Clinical Genome Resource. This article outlines current efforts to improve the interpretation of genetic testing and the role of standardizing and disseminating information. By assessing the strength of gene-disease associations, standardizing variant curation guidelines, sharing genomic data among expert members, and incorporating data from existing disease databases, the number of variants of uncertain significance will decrease, thereby improving the value of genetic testing as a diagnostic tool.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Blood Platelet Disorders* / diagnosis
  • Blood Platelet Disorders* / genetics
  • Female
  • Genetic Diseases, Inborn* / diagnosis
  • Genetic Diseases, Inborn* / genetics
  • Genetic Testing*
  • Hemorrhage* / diagnosis
  • Hemorrhage* / genetics
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Thrombosis* / diagnosis
  • Thrombosis* / genetics