Loading
A variant of uncertain significance (VUS) is a genetic change that has been found but nobody yet knows whether it matters.
A variant of uncertain significance (VUS) is a genetic change that has been detected but whose effect on disease is not yet known. Such findings are common on germline panels and in tumour sequencing, and they should not drive treatment decisions; over time many are reclassified through ClinVar, functional assays and population data. The term is linked to the Germline (hereditary) testing and Comprehensive genomic profiling technologies, to the ClinVar collection and AlphaMissense, and to the terms Mutation, Genomic profiling and Hereditary cancer syndromes. It appears in the bottleneck on unidentified inherited risk, and ideas that respond to it include testing every possible mutation in every cancer gene so no result is uncertain, and a plain-language version of every genomic report.
Showing the technology this term belongs to: Germline (hereditary) testing.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
For TNBC, which is diagnosed young and is the PARP inhibitor-eligible subtype, the guideline makes germline testing part of the diagnostic workup rather than a referral decision.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
It turned a frequently reported variant into an interpretable one: the class decides whether the stain will be negative, how poor the prognosis is, and whether immunotherapy is more rather than less likely to help.
The broad-panel figure: one patient in five carries something inheritable, and about one in fifteen carries something treatable.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
It defines the gene list a TNBC germline panel should report on and shows the same genes apply in African American women, the population with the highest TNBC incidence.
Shares ClinVar, Mutation, Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference.
Shares Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Homologous recombination repair gene mutation in prostate cancer, Triple-negative breast cancer (TNBC).
Shares Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Homologous recombination repair gene mutation in prostate cancer, Prostate cancer, Colorectal cancer.
Shares Founder variant, Inherited risk is mostly unidentified, Germline (hereditary) testing, Pancreatic ductal adenocarcinoma.
Shares Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Homologous recombination repair gene mutation in prostate cancer, Prostate cancer, Colorectal cancer.
Shares Genomic profiling, Pancreatic ductal adenocarcinoma, Prostate cancer, Colorectal cancer.
Shares Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference, Circulating tumour DNA fraction (and what a negative plasma result means), Homologous recombination repair gene mutation in prostate cancer.
Shares Founder variant, Inherited risk is mostly unidentified, Germline (hereditary) testing.