When a family has a child with a rare undiagnosed condition, a woman is diagnosed with an aggressive form of breast cancer, or a couple is planning their next chapter, they want assurance that the diagnostic labs that are analyzing and interpreting their genetic tests are using reputable, trusted, and up-to-date resources. That’s why LabCorp, Genomics England, and other national reference laboratories use the Human Gene Mutation Database (HGMD) Professional.
The largest, expert-curated resource for finding disease-causing mutations, HGMD Professional gives diagnostic labs conducting germline NGS testing the best possible chance of confidently reaching a diagnosis.
Quality over quantity
Unlike new machine learning or artificial intelligence platforms that rapidly index millions of journal articles for mutations, HGMD Professional leverages human judgement and expertise—every catalogued mutation has been “touched” by a trained scientist to ensure accuracy, relevance, and context. Therefore, HGMD Professional does not contain erroneous information or include inferred genotypes (based on documented protein alterations) or inferred protein alterations (based on documented genotypes). It is the most trusted starting resource for answering the question, “Does this mutation cause human disease?”
“Next-generation sequencing has become a powerful tool to identify genetic variants that play a role in inherited diseases, providing a flexible technology platform that allows us to go from large-scale to highly targeted test panels that can be used for both clinical diagnostics and in studies of new therapies and diagnostics,” said Marcia Eisenberg, PhD and Chief Scientific Officer for LabCorp Diagnostics. “Having access to the most comprehensive and up-to-date catalogue of known mutations augments our existing variant classification expertise. This will allow us to continue to provide physicians and researchers with the best possible test interpretations, advancing LabCorp’s mission to improve health and improve lives.” Read the official press release here.
HGMD Professional by the numbers
- 314,000+ expert-curated disease-causing mutations
HGMD Professional is unique in that it not only catalogs disease-causing mutations in a centralized, easy-to-search database, it also provides users with detailed information about each mutation. For example, HGMD Professional provides information on genotype-phenotype relationships, literature references, HGVS descriptions, genomic coordinates, and, more recently, nucleotide-level annotations. This level of detail is not supported by AI-powered databases.
- 16,000+ peer-review papers cite the use of HGMD
Thousands of clinical labs use HGMD Professional as an important resource for their informatics pipeline. For example, in addition to LabCorp, Genomics England uses HGMD Professional in 13 NHS Genomic Medicine Centres to aid in the analysis and interpretation of NGS tests for rare, inherited diseases.
Expert curation vs. artificial intelligence
Today with the advent of digitalization, there are a number of “comprehensive genomic search engines” that tout artificial intelligence as the best way to identify and interpret pathogenic variants from large quantities of data. However, artificial intelligence does not compare or replace human judgment.
|Speed of curation
|Quality of data
|Reduced noise in data
|Identification of published errors
|Normalize to gene model (needed to compare mutations from different sources)
|Minimize artifact mutations
X = low | XXX = high | n/a = not capable
Why quality over quantity matters
In clinical diagnostic settings, labs cannot afford to misinterpret a mutation. While AI-powered databases offer greater curation speeds, they do so at a price: they only index articles (oftentimes just the abstracts), they do not re-classify mutations are more information comes to light, they have no way of reconciling discrepancies in variant reporting.
Discrepancies in variant reporting
HGMD curators note that approximately 20% of articles have discrepancies in variant reporting that require additional scrutiny. Of these, 25% can be resolved by utilizing other information reported in the manuscript or by referring to supplementary material. However, about 75% of these ambiguities necessitate direct contact with the authors . The HGMD curation team does contact authors directly if they encounter discrepancies in variant reports. AI-powered solutions do not offer this feature.
Try HGMD Professional for free
Want to try HGMD Professional in your lab? It’s easy and free! Simply fill out this form and one of our experts will get you set-up with HGMD Professional in your lab for up to 5 days.
Request your free trial of HGMD Professional here.
Have questions? Want to learn more? Check out our HGMD Professional resource hub here.
- Stenson, P.D., Mort, M., Ball, E.V. et al. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. Hum Genet 139, 1197–1207 (2020). https://doi.org/10.1007/s00439-020-02199-3