ClinVar is a public archive that compiles reports on human genetic variations and their connections to health conditions. Managed by the National Center for Biotechnology Information (NCBI), this database serves as a central repository for information about genetic changes and their impact on human health. It documents the relationships between a genetic variant and a health status, alongside the supporting evidence for those assertions. ClinVar aims to provide an understanding of how specific genetic variations relate to diseases or drug responses.
The Purpose of ClinVar
The primary goal of ClinVar is to gather genetic information from diverse sources into a single, standardized location. This aggregation includes data from clinical diagnostic laboratories, research studies, and expert panels. Before centralized databases, genetic variant information might have been known by a laboratory in one region but inaccessible elsewhere. ClinVar addresses this fragmentation by fostering data sharing among the global medical and research communities. This centralization helps standardize genetic variant interpretation, improving diagnostic accuracy and advancing knowledge about variations and associated conditions.
Understanding Variant Classifications
ClinVar classifies a genetic variant’s impact on health using standardized terms. These classifications are based on interpretations provided by submitters and represent the asserted relationship between a variant and a condition. There are five main categories used to describe a variant’s clinical significance.
A “Benign” classification indicates that the genetic variant is considered harmless and does not contribute to disease.
“Likely Benign” suggests that the variant is probably harmless, though there might be slightly less conclusive evidence than for a “Benign” classification.
A “Variant of Uncertain Significance” (VUS) means there is currently not enough information to determine if the genetic change is harmful or harmless. This classification often arises when a variant is newly discovered, or when existing evidence is insufficient or contradictory. For a patient, a VUS result means further research or additional family studies may be needed to clarify its role.
“Likely Pathogenic” indicates that the variant is probably disease-causing, with strong but not absolute evidence.
Finally, a “Pathogenic” classification signifies that the genetic variant is known to cause or significantly contribute to a specific disease. This determination is supported by robust scientific evidence from multiple studies.
How Information is Submitted and Reviewed
Information within ClinVar is contributed by various organizations, including clinical testing laboratories, research laboratories, and expert panels. These submitters provide their interpretations of genetic variants, often based on patient samples or research findings. Each submission includes a description of the variant, the condition it was interpreted for, the interpretation of its clinical significance, and supporting evidence.
To help users assess reliability, ClinVar employs a “review status” system, displayed as stars. A higher star rating indicates more evidence and consensus supporting a classification. For instance, a submission with one star means a single submitter provided criteria for their classification, while a four-star rating indicates the classification is supported by practice guidelines.
The database transparently displays “conflicting interpretations,” where different laboratories or groups may classify the same variant differently based on their available evidence. ClinVar aggregates these submitted records and calculates an overall interpretation, highlighting any disagreements among submitters. This transparency allows users to see the full spectrum of interpretations for a given variant.
Role in Clinical Practice and Research
ClinVar plays a role in both clinical practice and scientific research. Clinicians and genetic counselors use ClinVar to interpret a patient’s genetic test results. Accessing the aggregated data and classifications helps healthcare professionals understand the potential health implications of a detected genetic variant, which aids in diagnosing genetic conditions and guiding patient care. This tool helps them determine if a variant found in a patient’s DNA is known to be associated with a disease or if its significance is still uncertain.
Researchers also use the extensive data within ClinVar to advance scientific understanding. The aggregated information helps them identify new connections between specific genes and diseases, leading to a deeper understanding of disease mechanisms. Scientists can analyze patterns across numerous variants and conditions, which contributes to the broader knowledge base in human genetics and can inform the development of new diagnostic methods or therapies.