title: Meeting the challenges of interpreting variants of unknown clinical significance in BRCA testing.
abstract: Many BRCA1 and BRCA2 genetic mutations are known to result in an elevated breast cancer risk. Routine BRCA1/2 gene screening is offered to patients thought to have an increased risk of carrying a deleterious mutation. 5-10% of genetic tests identify a variant of unknown clinical significance (VUCS), creating significant challenges to health care providers. Recent advances in sequencing technologies allow more genes to be screened in an increasing number of individuals and at an ever decreasing cost. Significantly more VUCS will be identified, adding to the uncertainty of how to manage these patients. The addition of splicing assays to current variant classification tools may be instrumental towards understanding the disease risk of these variants and improve the reliability of these assays.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lattimore
authors.forename: Margaret
authors.initials: M
authors.lastname: Currie
authors.forename: Caroline
authors.initials: C
authors.lastname: Lintott
authors.forename: Jan
authors.initials: J
authors.lastname: Sullivan
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Robinson
authors.affiliation: Senior Research Fellow, Pathology department, Otago University Christchurch, 2 Riccarton Ave, Christchurch, 8011, New Zealand. logan.walker@otago.ac.nz.
authors.forename: Logan C
authors.initials: LC
authors.lastname: Walker
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D024522:Genes, BRCA2 / Q000502:physiology*; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D009520:New Zealand; D058996:Quality Improvement; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods / Q000592:standards