The Human Gene Mutation Database: 2008 update

By Peter D. Stenson, Matthew E. Mort, Edward V. Ball, K. Howells, A. Phillips, Nick S. T. Thomas, David N. Cooper. 2009

907 citations recorded by the source corpus.

The Human Gene Mutation Database (HGMD®) is a comprehensive core collection of germline mutations in nuclear genes that underlie or are associated with human inherited disease. Here, we summarize the history of the database and its current resources. By December 2008, the database contained over 85,000 different lesions detected in 3,253 different genes, with new entries currently accumulating at a rate exceeding 9,000 per annum. Although originally established for the scientific study of mutational mechanisms in human genes, HGMD has since acquired a much broader utility for researchers, physicians, clinicians and genetic counselors as well as for companies specializing in biopharmaceuticals, bioinformatics and personalized genomics. HGMD was first made publicly available in April 1996, and a collaboration was initiated in 2006 between HGMD and BIOBASE GmbH. This cooperative agreement covers the exclusive worldwide marketing of the most up-to-date (subscription) version of HGMD, HGMD Professional, to academic, clinical and commercial users.

Subfields: Cancer Research, Genetics, Molecular Biology

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Citations in the corpus

A general framework for estimating the relative pathogenicity of human genetic variants (2014, methodology): “…shows violin plots of the median C-scores of potential nonsense (stop-gained) variants for genes that: harbor at least 5 known pathogenic mutations 48 (“disease”); are predicted to be “essential” 23 ; harbor variants associated with complex traits 41 (“GWAS”); harbor at least 2 loss-of-function…”
SIFT web server: predicting effects of amino acid substitutions on proteins (2012, methodology): “SIFT Indel was trained on a set of disease-causing frameshifting indels (3) and neutral indels derived from the UCSC pairwise alignments of the human genome with mammalian genomes (35).”
The Human Gene Mutation Database (HGMD) and Its Exploitation in the Fields of Personalized Genomics and Molecular Evolution (2012, background): “The Human Gene Mutation Database (HGMD) represents the only comprehensive collation of germ-line mutations underlying human inherited disease (Stenson et al., 2009).”
Deep mutational scanning: assessing protein function on a massive scale (2011, background): “For example, non-synonymous mutations in protein coding sequences account for ~57% of the mutations known to be involved in human disease [1].”
dbNSFP: A Lightweight Database of Human Non-synonymous SNPs and Their Functional Predictions (2011, background): “As evidence, NSs constitute more than half of the entries of disease-causing genetic changes in the Human Gene Mutation Database (HGMD) [Stenson et al., 2009].”
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge (2014, methodology): “Use of splice prediction tools is particularly important, as approximately 14% to 15% of all hereditary disease alleles are annotated as splicing mutations [55].”
Countering GATTACA: efficient and secure testing of fully-sequenced human genomes (2011, background): “G, or T) differs between members of the same species or paired chromosomes of an individual [68].”
A new disease-specific machine learning approach for the prediction of cancer-causing missense variants (2011, background): “The manually curated SwissVar database [10] reports the possible pathologic effect of about 61,000 missense SNPs and the public version of the HGMD database [11] includes more than 74,000 mutations causing or associated with human inherited disease, plus disease-associated/functional polymorphisms.”
Predicting the Functional Effect of Amino Acid Substitutions and Indels (2012, background): “3), at the gene sequence level approximately half of the human disease variations are associated with single nucleotide substitutions (57%), and close to one-fourth of disease mutations (22%) are associated with small indels [16,17].”
In silico prediction of splice-altering single nucleotide variants in the human genome (2014, methodology): “Dataset, in silico tools and missing score rates After filtering data according to our inclusion and exclusion criteria, 1164 unique splice-altering scSNVs within 408 genes from three databases constituted our positive group, among which 790 were from HGMD (8), 266 from the SpliceDisease database (2”
Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing (2011, background): “Given that the Human Gene Mutation Database (HGMD) lists 102,433 disease mutations (27), a number that is steadily increasing, a fixed-content method appeared impractical.”
The human splicing code reveals new insights into the genetic determinants of disease (2014, methodology): “The model was further evaluated using genome-wide SNVs, including common SNPs in dbSNP135 (16), point mutations in HGMD (17), and rare variants from ANNOVAR (54).”
Insights into hominid evolution from the gorilla genome sequence (2012, background): “In several cases, a protein variant thought to cause inherited disease in humans 32 is the only version found in all three gorillas for which we have genome-wide sequence data (Supplementary Table 8.9).”
Automated inference of molecular mechanisms of disease from amino acid substitutions (2009, background): “Currently, there are over 50 000 coding region mutations, causing or associated with human genetic disease, listed in the Human Gene Mutation Database (HGMD) (http://www.hgmd.org; Stenson et al., 2009), of which ∼40 000 are amino acid substitutions.”