The current state of clinical interpretation of sequence variants.
Accurate and consistent variant classification is required for Precision Medicine. But clinical variant classification remains in its infancy. While recent guidelines put forth jointly by the American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) for the classification of Mendelian variants has advanced the field, the degree of subjectivity allowed by these guidelines can still lead to inconsistent classification across clinical molecular genetic laboratories. In addition, there are currently no such guidelines for somatic cancer variants, only published institutional practices. Additional variant classification guidelines, including disease- or gene-specific criteria, along with inter-laboratory data sharing is critical for accurate and consistent variant interpretation.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, 65 Landsdowne Str., Cambridge, MA 02115 USA.
Derick C
DC
Hoskinson
Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, 75 Francis Str., Boston, MA 02115 USA.
Adrian M
AM
Dubuc
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, 65 Landsdowne Str., Cambridge, MA 02115 USA; Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, 75 Francis Str., Boston, MA 02115 USA. Electronic address: hmason-suares@partners.org.
Heather
H
Mason-Suares
D030541:Databases, Genetic; D005820:Genetic Testing; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000639:trends; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine; D017422:Sequence Analysis, DNA / Q000639:trends*