The Summer 2020 Release of the Human Gene Mutation Database (HGMD) Professional is available, expanding the world’s largest collection of human inherited disease mutations to 289,346 entries–that’s 6,451 more than the previous release.
For over 30 years, HGMD Professional has been used worldwide by researchers, clinicians, diagnostic laboratories and genetic counselors as an essential tool for the annotation of next-generation sequencing (NGS) data in routine clinical and translational research. Founded and maintained by the Institute of Medical Genetics at Cardiff University, HGMD Professional provides users with a unique resource containing expert-curated mutations all backed by peer-reviewed publications where there is evidence of clinical impact.
Whether searching for an overview of known mutations associated with a particular disease, interpreting clinical test results, looking for the likely causal mutation in a list of variants, or seeking to integrate mutation content into your custom NGS pipeline or data repository—HGMD is the defacto-standard repository for heritable mutations that can be adapted to a broad range of applications.
detailed mutation reports
new mutation entries in 2019 alone
summary reports listing all known
inherited disease mutations
HGMD is powered by a team of expert curators at Cardiff University. Data are collected weekly by a combination of manual and computerized search procedures. In excess of 250 journals are scanned for articles describing germline mutations causing human genetic disease. The required data are extracted from the original articles and augmented with the necessary supporting data.
The number of disease-associated germline mutations published per year has more than doubled in the past decade (Figure 1). As rare and novel genetic mutations continue to be uncovered, having access to the latest scientific evidence is critical for timely interpretations of next-generation sequencing (NGS) data.
View the complete HGMD Professional statistics here.
Read more about the importance of having access to the most up-to-date and comprehensive database for human disease mutations in our white paper.
HGMD Professional helps clinical testing labs analyze and annotate next-generation sequencing (NGS) data with current and trusted information. Unlike other mutation databases, HGMD mutations are all backed by peer-reviewed publications where there is evidence of clinical impact.
To get the most out of your HGMD Professional subscription, visit our Resources webpage for case studies, technical notes, and video tutorials
NEW! HGMD on-demand webinar
In our new on-demand webinar, you will discover the power of HGMD Professional and see why reference labs around the world, such as LabCorp and Genomics England, use HGMD Professional in their clinical test interpretation. Through a live demonstration, you will learn how to use the online interface and downloadable database, as well as how to use HGMD Professional and ANNOVAR to produce a powerful in-house variant interpretation solution.
Watch the webinar here.
An updated version of ANNOVAR is also available.
Learn more about how ANNOVAR can be used with HGMD for variant annotation. Watch a recorded webinar featuring ANNOVAR here.
The Genome Trax™ 2020.2 is now available. Updated tracks have been released with HGMD 2020.1 content for all HGMD-related tracks. Additional major updates include TRANSFAC® release 2020.2, and PROTEOME™ release 2020.2.
For labs looking to generate clinician-grade reports for germline or somatic NGS testing, QIAGEN Clinical Insight (QCI) Interpret reproducibly translates highly complex NGS data into standardized reports using current clinical evidence from the QIAGEN Knowledge Base, which consists of over 40 public and proprietary databases, including HGMD Professional.
Click here for a free demonstration of QCI Interpret.
The winter release of HGMD Professional now contains a total of 220,270 mutation entries. That’s 6,112 more mutation entries than the previous release. Unlike other mutation databases, HGMD mutations are all backed by peer-reviewed publications where there is evidence of clinical impact.
View the complete HGMD statistics.
New HGMD feature
HGVS nomenclature has been added for the non-coding micro-lesions and regulatory substitutions.
HGMD Professional is one of the most valuable resource in variant interpretation and research. Click here to download our white paper on how HGMD Pro helps clinical labs avoid the clinical blind spot which providing the most comprehensive resource for published, disease-causing, germline mutations.
There are no new updates with ANNOVAR with this release.
Learn more about how ANNOVAR can be used with HGMD for variant annotation.
Updated tracks have been released concurrent with the HGMD release for all HGMD-related tracks. Additional major tracks updated include TRANSFAC® release 2017.3, PROTEOME™ release 2017.3. Release notes can be found here.
The fall release of HGMD Professional now contains a total of 214,158 mutation entries. That’s 5,790 more mutation entries than the previous release. Unlike other mutation databases, HGMD mutations are all backed by peer-reviewed publications where there is evidence of clinical impact.
View the complete HGMD statistics
New HGMD feature
The original extended cDNA sequences were only available for a small number of genes, and have been out of date for some time. We have now added a link to a new extended cDNA sequence for each gene based on hg38 sequence and annotations. The sequence is shown split between the full exonic sequence in uppercase, and 50 bp of flanking intronic sequence in lowercase. Exon numbering is sequential. This feature is under ongoing development, and we plan to add in further CDS annotations at a later date. The old extended cDNA sequences, along with the old mutation viewer will be removed from HGMD Professional for the 2018.1 release.
If you are interested into a clinical-grade pathogenicity assessment for a given variant implementing the ACMG guidelines and including additional supporting data such as case counts in a hereditary cancer context, we recommend you take a look at QIAGEN Clinical Insight for Hereditary Cancer, which includes HGMD. The following is a table summarizing key features between HGMD Public, Pro, and QIAGEN Clinical Insights (QCI).
2017 July 16
ANNOVAR new version is available now! You can use the old link to download, or you can register again to get download email. This release contains some minor fixes and improvements: fixed a bug in calculating upstream distance that print when -separate is specified in annotate_variation.pl, improvements to coding_change.pl to report more stopgain/stoploss and fix use-of-uninitialized-value issue, slight change to convert2annovar.pl to handle mal-formed VCF file.
2017 September 12
There is now an hg38 version of ensGene available through ANNOVAR directly so that users do not need to build it themselves.
2017 September 29
2017Sep29: avsnp150 is available through ANNOVAR now in hg19 and hg38 coordinate, to annotate your variants with dbSNP identifiers.
2017 October 13
Latest clinvar (20170905) is available now through ANNOVAR in hg19 and hg38 coordinates. A long-standing problem on multi-allelic variants in ClinVar is now addressed, so that multi-allelic variants are now correctly assigned to the corresponding benign/pathogenic categories. The 20170130/20170501 versions are also updated to resolve this issue.
Learn more about how ANNOVAR can be used with HGMD for variant annotation.
Updated tracks have been released concurrent with the HGMD release for all HGMD-related tracks. Additional major tracks updated include TRANSFAC® release 2017.3, and PROTEOME™ release 2017.3. Release notes can be found here.
Next-generation sequencing, bolstered by powerful data analytics and the clinical interpretation of genetic variants in a patient’s cancer, is on the cusp of transforming healthcare. We are at a watershed moment in medical history, comparable to the discovery of microorganisms, the development of vaccines, and the creation of antibiotics.
Precision medicine promises a paradigm shift in care delivery, one that removes the need for guesswork, variable diagnoses, and treatment strategies based on generalized demographics. Consider the tumor, for example. Once believed to be a uniform mass of malignancy, the tumor is now known to have tremendous genetic diversity, driven by a wide range of genetic mutations. Scientists continue to identify more and more of these mutations, which is crucial to the development of more targeted, and potentially much more effective, therapies. With therapies that go after mutations at the molecular level, there will inherently be better patient outcomes.
Yet, the progress of precision medicine now depends largely on getting data from discoveries into the hands of the doctors on the front lines of patient care. This is where QIAGEN Clinical Insight™ (QCI) is leading the way for predictive and preventative care. Below is a list of five trends shaping the precision medicine transformation and how QCI is tackling each challenge and opportunity.
Later-stage melanoma, colorectal, and lung cancer patients are now routinely offered DNA-based molecular diagnostic, theranostic, and prognostic tests. With the commonality of molecular diagnostic testing, numerous medical institutions are attempting to develop in-house testing capabilities. QCI enables molecular diagnostic labs and healthcare providers to develop and operationalize scalable, compliant, and secure molecular and genomic data analysis, interpretation, and reporting solutions to implement genomics-guided clinical decision support at the point of care.
Understanding the differences in genomic results between different tumor profiling approaches will become increasingly important as the cancer genome is leveraged to stratify patients for new therapeutic strategies. However, the translation of results by community oncologists remains a major hurdle in the stratification of cancer into subtypes. A unique capability of QCI is the ability to recognize and interpret genetic factors that span multiple variants. Unlike alternative approaches that interpret a patient’s genetic profile on a variant-by-variant basis, QCI Interpret assesses the genetic profile in its entirety, matching combination variants that can influence the selection of an appropriate treatment or clinical trial.
Recent literature signals a growing paradigm shift toward integrating therapeutics and diagnostics, rather than developing them separately. In this gradual move toward more effective and personalized medications, “theranostics” is expected to increase response rates and improve patient outcomes. Yet, we continue to see variability in targeted therapy and trial matching. The QCI platform is a potent tool that evaluates genomic variants comparing them with published biomedical literature, professional association guidelines, publicly available databases and annotations, drug labels, and clinical trials. With QCI, clinicians will be able to rapidly classify variants, identify treatment options, and perform geographical clinical trial matching.
“Interpretation” remains the rate-limiting factor for the adoption and benefits of genomics-guided clinical decision support at the point of care; but, labs continue to invest a majority of their time and resources in instrument and assay selection. QCI shifts the focus from instrumentation to insight, catalyzing the rate of discovery and deployment of precision medicine capabilities. QIAGEN has developed the only publically available, industrial-scale, clinical-grade technology platform that can cost-effectively enable this capability for NGS testing laboratories. Thanks to an army of expert PhD curators, the QIAGEN Knowledge Base allows physicians and oncologists to develop patient-specific recommendations in the context of over 13 million relevant biomedical findings.
A recent U.S. Food and Drug Administration working group identified the need for improving standards of automated clinical NGS analysis, interpretation, and reporting policies. Widespread adoption of these guidelines will enhance communication between molecular pathologists, oncologists, and geneticists, as well as enhance patient care. QCI assists with the standardization of NGS analytical workflows by supporting virtually any clinical testing laboratory in developing and implementing a robust production pipeline for its cancer patient population.
Like nearly all aspects of healthcare, reaching the full potential of precision medicine will require collaboration among multiple players and a shift in current thinking: from information to insight. QCI is designed to fit into the clinical care workflow, which simplifies the adoption of precision medicine by delivering high-quality, scientific research to the bedside to improve patient care and outcomes.
By advancing the pace of precision medicine with QCI, any organization can harness the power of precision medicine to improve population health worldwide.
Learn more about QIAGEN Clinical Insight
The summer release of HGMD Professional now contains a total of 208,368 mutation entries. That’s 4,483 more mutation entries than the previous release. Unlike other mutation databases, HGMD mutations are all backed by peer-reviewed publications where there is evidence of clinical impact.
View the complete HGMD statistics
New HGMD feature
The original mutation viewer no longer reliably functions in many web browsers due to support for NPAPI being dropped by several vendors. There is a replacement now available (link via the HGMD gene home pages) which maps coding region mutations on to the HGMD cDNA sequence, via the cDNA page. This feature is under ongoing development.
If you are interested into a clinical-grade pathogenicity assessment for a given variant implementing the ACMG guidelines and including additional supporting data such as case counts in a hereditary cancer context, we recommend you take a look at QIAGEN Clinical Insight for Hereditary Cancer, which includes HGMD. The following is a table summarizing key features between HGMD Public, Pro, and QIAGEN Clinical Insight (QCI).
The following new database updates have been made available in ANNOVAR since the last release announcement.
Updated tracks have been released concurrent with the HGMD release for all HGMD-related tracks. Additional major tracks updated include TRANSFAC® release 2017.2, and PROTEOME™ release 2017.2. Release notes can be found here.
Note: This release will be available from July 7, 2017.
Research scientist Dr. Margarete Odenthal leads the translational molecular pathology group at University Hospital Cologne, putting new technologies through their paces to determine which ones best fit the needs and workflows of the diagnostics lab. Recently, she has worked closely with QIAGEN to assess sample extraction, target enrichment, and library preparation kits as well as data analysis and interpretation tools in a variety of cancer studies.
In one NGS-based study, she and her team analyzed BRCA1 and BRCA2 mutations in samples from severe ovarian cancer using QIAGEN products for library preparation, amplicon sequencing, and data analysis. Odenthal began with macrodissected FFPE ovarian cancer samples, which carried known germline point mutations or large deletions in the BRCA genes, using the GeneRead DNAseq Targeted Panels for human BRCA1 and BRCA2 exons for target enrichment. After sequencing, results were analyzed with Biomedical Genomics Workbench to identify somatic pathogenic mutations. “We used the copy number variation tool in order to see big deletions in the BRCA1 and BRCA2 genes,” Odenthal says. “Normally you don’t see these deletions very easily, so people have found this quite interesting.” By using the analysis tool to detect large deletions, her team is able to quickly evaluate pathogenic mutations likely to damage the protein.
In other work, she has been focused on new approaches to make sense of tumor activity that cannot be explained by DNA mutations alone. “In these cases, the tumor driving force might be less about mutations and more about different expression and splicing patterns,” Odenthal says. “There are some transcripts which are alternatively spliced and have a more oncogenic version of the protein.” Having this information can be relevant for decisions about which therapy to use, so Odenthal has been using a cohort of prostate cancer samples as the foundation for studies of DNA and RNA together. “QIAGEN has good chemistry to see the DNA mutations and in parallel to look at splicing variants and expression,” she notes.
In this pipeline, she combines DNA and cDNA in a single sequencing run. “You do the mutation and expression analysis in one workflow and you have everything together. I think modern pathology has to have everything in one pipeline,” Odenthal says. She believes that running separate FISH, NGS, and DNA promoter methylation analysis workflows will not be sustainable as diagnostic labs continue to ramp up their capacity. “It is much more efficient to have one workflow and get all this information,” she adds.
To learn more about how Dr. Odenthal has used QIAGEN Bioinformatics tools, read the full case study here.
Photo credit: Uniklinik Köln
HGMD® is widely accepted as the gold standard for information about published inherited disease mutations, but what makes it such a great resource? In short, it’s HGMD’s comprehensive literature coverage. But what does comprehensive mean, and is it really a big deal?
Comprehensive means identifying every published article that describes a germline mutation and assessing whether the mutation has been convincingly demonstrated to be associated with a specific disease or phenotype. If the association is convincing, and the mutation has not been previously reported in HGMD, a new entry will be created. Likewise, if the article provides information that calls a previously reported association into doubt or provides information about a new associated phenotype for an existing mutation, the information is captured and added to HGMD.
Just picture the effort that it has taken to curate the more than 70,000 published articles describing the greater than 170,000 mutation entries cataloged in HGMD today. And then consider that the work is never ending. New papers describing new mutations are published every week. And in fact the rate of publication of new mutations is only increasing as NGS technologies have helped advance the pace of discovery. As the figure below shows, in less than a decade the number of new mutations described in the literature for a single year has more than doubled. That’s a lot more articles to read than ever before.
What does this mean for you? It means that you can confidently use HGMD to substantially decrease the time it takes to search for and collect information about inherited disease mutations in the published scientific literature. It takes less than five minutes to search HGMD for a disease and return the list of associated mutations. Compare that to the time it would take to comb through a typical list of articles returned by a PubMed search. At a very conservative five minutes per article, the savings for a moderately well studied disease such as Bloom Syndrome could be more than 7 hours. For a very well studied disease like Cystic Fibrosis the savings could be upwards of 250 hours. That’s the advantage of comprehensive coverage.
Learn more about HGMD
This webinar highlights our highly accurate and integrated end-to-end NGS analysis solution for the discovery of novel, and clinically relevant, rare and inherited disease causing variants, from various sample types in just one step.
Dr. Anika Joecker, Global Product Manager, presents the easy to use end-to-end hereditary disease workflows in Biomedical Genomics Workbench and Ingenuity Variant Analysis, as well as the Allele Frequency Community – an extensive, high-quality, ethnically diverse collection of human allele data for use as a reference set. The presentation will also touch upon the impact of accuracy and time-savings associated with reducing the number of false positives when searching for disease causing mutations in NGS data.
If you'd like to know more about how our hereditary disease solution addresses the NGS analysis bottleneck by delivering seamless and highly accurate end-to-end workflows for the identification and interpretation of causal variants you should read our recent press release. A laboratory using this new hereditary disease solution can achieve a case solve rate as high as 100%, while significantly reducing the rate of irrelevant variants for follow-up by 98% to 100%. These close to perfect solve rates are not possible using any other bioinformatics solution available in the market today, according to the latest benchmarking study that we presented at ASHG. The solution is cost-effective and can handle a high volume of samples (for example, 18,000 whole genomes per year).
Biomedical Genomics Workbench
Ingenuity Variant Analysis
Press release: QIAGEN launches new bioinformatics solution hereditary diseases
