# Variant of uncertain significance (VUS)

Source: https://onco.cc/terms/vus/  
OnCo record `vus` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A variant of uncertain significance (VUS) is a genetic change that has been found but nobody yet knows whether it matters.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-04

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Variant_of_uncertain_significance
- Wikipedia: https://en.wikipedia.org/wiki/Variant_of_uncertain_significance

## Connected records

- technologies: [AlphaMissense](https://onco.cc/technologies/alphamissense/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- key papers: [Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference](https://onco.cc/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/), [Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline](https://onco.cc/key-papers/paper-bedrosian-asco-sso-germline-testing-breast-jco-2024/), [Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms](https://onco.cc/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/), [The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer](https://onco.cc/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/), [The long tail of oncogenic drivers in prostate cancer](https://onco.cc/key-papers/paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018/), [Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing](https://onco.cc/key-papers/paper-shimelis-tnbc-risk-genes-jnci-2018/)
- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/)
- terms: [Founder variant](https://onco.cc/terms/founder-variant/), [Genomic profiling](https://onco.cc/terms/genomic-profiling/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Mutation](https://onco.cc/terms/mutation/)
- collections: [ClinVar](https://onco.cc/collections/clinvar/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/)
- ideas: [Every pathology and genomic report ships with a signed plain-language version](https://onco.cc/ideas/idea-moon-results-in-plain-words/), [Test every possible mutation in every cancer gene so no result is 'uncertain'](https://onco.cc/ideas/idea-prev-vus-saturation-editing-consortium/)
- institutions: [Wellcome Sanger Institute](https://onco.cc/institutions/wellcome-sanger/)
- pathways: [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/)

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JSON: https://onco.cc/api/v1/entities/vus.json