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Developing the Human Gene Mutation Database into an international resource for improved diagnosis of diseases


Adding content and functionality to the Human Gene Mutation Database (HGMD) database has further secured its role as the key global tool for genetic research.

The HGMD was first established by Cardiff University research in 1996, and is the first and only fully curated, annotated collection of inherited disease-causing mutations in nuclear genes, made up of pathologically relevant mutation data.

Since 2000, the HGMD has been developed into a valuable scientific resource and is employed worldwide by over 700 organisations in public health and commercial settings, ensuring rapid and accurate test results in both clinical diagnostics and personalised genomics.

Genetic research

Following an increase in data from 2005, the database became the central unified repository for disease-related genetic variation in the germline, with over 9,000 new entries per year by the Cardiff University team.

The regular updates to the database have made it of use beyond academia, in particular of use by human molecular geneticists, genome scientists, molecular biologists, clinicians, and genetic counsellors, as well as researchers specialising in biopharmaceuticals, bioinformatics and personalised genomics.

Expansion and development

Cardiff University has licenced the HGMD to commercial partner QIAGEN, and it has now become the primary disease-associated mutation database used by the international biomedical and clinical community. QIAGEN currently has more than 600 HGMD Professional subscribers across 51 countries worldwide.


Dr Frank Schacherer, VP Products and Solutions at QIAGEN, confirmed that the customer base has continued to grow, and the compound annual growth rate of sales over the last five years was in the double digits, “thanks to the University’s commitment to keep the database current, comprehensive and competitive”.

At a national level, Genomics England (set up and owned by the Department of Health and Social Care) uses HGMD Professional to deliver the 100,000 Genomes Project. This project has sequenced 100,000 whole genomes from NHS patients with rare diseases and common cancers (around 25,000 patients), as well as their families and a control group of volunteers with no known genetic condition.

As of March 2019, potential diagnoses were identified for approximately 3,300 (1 in 5) of the rare disease sufferers enrolled in the programme, and for around 40% of those with intellectual disabilities. Clinical trials or more effective medicines were also identified for around half of the cancer patients enrolled (approximately 12,500 patients), enhancing their care and increasing the chances of survival.

“As the global use of genomics in research and development has increased, the Cardiff team has added content and functionality to HGMD to maintain its relevance and increase its utility.”
Dr Frank Schacherer, VP Products and Solutions at QIAGEN

The HGMD has also contributed to the development of the computational model MutPred at Cardiff University, which predicts changes in protein sequences as a consequence of genetic mutation. First published in 2009, MutPred was independently confirmed to be one of the best performing mutation pathogenicity prediction methods available. The latest version, MutPred2, was shown to identify structural and functional mutational signatures relevant to Mendelian disorders (disorders inherited through a genetic mutation in both parents, such as Duchenne Muscular Dystrophy, cystic fibrosis or sickle cell disease) as well as mutations associated with complex neurodevelopmental disorders.

To increase the usability for clinical groups and bioinformaticians, HGMD data formats have also been adapted to integrate with next-generation sequencing (NGS). NGS results can be directly compared with HGMD data, with relevant variants that have previously been implicated in disease causation highlighted. This advance in the database has improved the usability of HGMD data and greatly increased the computational analyses that could be applied, enhancing application in clinical settings.

Key results

The database is designed to speed up the research process for users, to quickly absorb the very latest gene reports on their area of interest.

A 2016 survey revealed that users access the database to save time trawling through literature, to determine if an identified mutation had been previously published, and to quickly find known mutations for a specific gene, solving challenges such as workflow bottlenecks, delayed processing of patient samples, and prioritising correct mutations.

By the end of 2020, the HGMD contained over 307,000 manually curated mutation reports covering more than 12,000 genes, which have been published in over 3,000 peer-reviewed journals.

Approximately 30,000 mutation entries are currently being added to the database per annum, and cDNA reference sequences are now available for 98% of listed genes.

Around 150,000 registered academic users can access a public version of HGMD for free, with a subscription version (HGMD Professional) distributed through QIAGEN GmbH via a Licence Agreement with Cardiff University.

Distribution was initially through the organisation BIOBASE, until QIAGEN GmbH’s acquisition of BIOBASE in May 2014. In July 2014, QIAGEN signed an agreement with BGI Tech Solutions Ltd, a subsidiary of BGI Group, the largest genomics organisation in the world.

Under the terms of the agreement, BGI now provide HGMD data to the Greater China (Mainland China, Hong Kong, Macau, Taiwan) market as a distributor and provide first level support for the database within this market.

In addition to this, LabCorp, one of the largest clinical laboratory networks in the world, incorporated HGMD within their QIAGEN Clinical Insight licence in 2019 to improve identification and interpretation of genetic variants within inherited diseases.

Genomic research

Key facts

  • The value of the HGMD was illustrated by a collaborative study involving Cardiff University and US collaborators. The project demonstrated that individuals unselected for disease harboured disease-causing mutations associated with a phenotype either in themselves or their family more frequently than had been previously assumed, with similar results found during a collaboration with the 1,000 Genomes Pilot Project.
  • Subscribers who use HGMD Professional to accelerate their diagnostic approaches, include John Hopkins University, Baylor College of Medicine, Mayo Clinic, MD Anderson Cancer Center, Scripps Research Institute, and the Children’s Hospital of Philadelphia.
  • HGMD data are used across the UK for diagnosis and prioritisation of candidate genes for disease analysis in a variety of NHS hospitals and foundations, including the Royal Brompton, Addenbrooke’s, and Great Ormond Street.