LOVD v.2.0: The next generation in gene variant databases

Center of Human and Clinical Genetics, Department of Human Genetics, Leiden University Medical Center, Leiden, Nederland.
Human Mutation (Impact Factor: 5.14). 05/2011; 32(5):557-63. DOI: 10.1002/humu.21438
Source: PubMed


Locus-Specific DataBases (LSDBs) store information on gene sequence variation associated with human phenotypes and are frequently used as a reference by researchers and clinicians. We developed the Leiden Open-source Variation Database (LOVD) as a platform-independent Web-based LSDB-in-a-Box package. LOVD was designed to be easy to set up and maintain and follows the Human Genome Variation Society (HGVS) recommendations. Here we describe LOVD v.2.0, which adds enhanced flexibility and functionality and has the capacity to store sequence variants in multiple genes per patient. To reduce redundancy, patient and sequence variant data are stored in separate tables. Tables are linked to generate connections between sequence variant data for each gene and every patient. The dynamic structure allows database managers to add custom columns. The database structure supports fast queries and allows storage of sequence variants from high-throughput sequence analysis, as demonstrated by the X-chromosomal Mental Retardation LOVD installation. LOVD contains measures to ensure database security from unauthorized access. Currently, the LOVD Website ( lists 71 public LOVD installations hosting 3,294 gene variant databases with 199,000 variants in 84,000 patients. To promote LSDB standardization and thereby database interoperability, we offer free server space and help to establish an LSDB on our Leiden server.
Hum Mutat 32:1–7, 2011.

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    • "Classifications for LOVD are defined as follows: B+^ is pathogenic, B+?^ is probably pathogenic, B?^ is effect unknown, B-^ is no known pathogenicity, and B-?^ is probably no pathogenicity. All classifications are listed in the format BReported/Concluded^, although for all variants in this data set, the Concluded classification was B?^ (Fokkema et al. 2011). A VUS classification in UMD is defined as B3—UV^, referring to Buncertain variant^ (Beroud et al. 2000). "
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    ABSTRACT: Genetic variants of uncertain clinical significance (VUSs) are a common outcome of clinical genetic testing. Locus-specific variant databases (LSDBs) have been established for numerous disease-associated genes as a research tool for the interpretation of genetic sequence variants to facilitate variant interpretation via aggregated data. If LSDBs are to be used for clinical practice, consistent and transparent criteria regarding the deposition and interpretation of variants are vital, as variant classifications are often used to make important and irreversible clinical decisions. In this study, we performed a retrospective analysis of 2017 consecutive BRCA1 and BRCA2 genetic variants identified from 24,650 consecutive patient samples referred to our laboratory to establish an unbiased dataset representative of the types of variants seen in the US patient population, submitted by clinicians and researchers for BRCA1 and BRCA2 testing. We compared the clinical classifications of these variants among five publicly accessible BRCA1 and BRCA2 variant databases: BIC, ClinVar, HGMD (paid version), LOVD, and the UMD databases. Our results show substantial disparity of variant classifications among publicly accessible databases. Furthermore, it appears that discrepant classifications are not the result of a single outlier but widespread disagreement among databases. This study also shows that databases sometimes favor a clinical classification when current best practice guidelines (ACMG/AMP/CAP) would suggest an uncertain classification. Although LSDBs have been well established for research applications, our results suggest several challenges preclude their wider use in clinical practice. Electronic supplementary material The online version of this article (doi:10.1007/s12687-015-0220-x) contains supplementary material, which is available to authorized users.
    Journal of community genetics 03/2015; 6(4). DOI:10.1007/s12687-015-0220-x
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    • "Locus specific databases (see for a comprehensive list) and " whole-genome " mutation databases such as HGMD [33], ClinVar [34], LOVD [35], and OMIM [36] are very informative resources for this task. Finding no previously identified variants indicates a novel variant in the proband analysed. "
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    ABSTRACT: Recent technological advances have created challenges for geneticists and a need to adapt to a wide range of new bioinformatics tools and an expanding wealth of publicly available data (e.g., mutation databases, and software). This wide range of methods and a diversity of file formats used in sequence analysis is a significant issue, with a considerable amount of time spent before anyone can even attempt to analyse the genetic basis of human disorders. Another point to consider that is although many possess " just enough " knowledge to analyse their data, they do not make full use of the tools and databases that are available and also do not fully understand how their data was created. The primary aim of this review is to document some of the key approaches and provide an analysis schema to make the analysis process more efficient and reliable in the context of discovering highly penetrant causal mutations/genes. This review will also compare the methods used to identify highly penetrant variants when data is obtained from consanguineous individuals as opposed to nonconsanguineous; and when Mendelian disorders are analysed as opposed to common-complex disorders.
    BioMed Research International 03/2015; DOI:10.1155/2015/923491 · 1.58 Impact Factor
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    • "538 cases were collected in The First Affiliated Hospital of Sun Yat-sen University, while 500 cases were obtained from an open-access internet database -Leiden Muscular Dystrophy pages ( [25] [26]. Multiplex probe ligation-dependent amplification (MLPA) was used for genetic testing in patients. "
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    ABSTRACT: The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD) and Becker (BMD) muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD), spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin - those that bind associated proteins of the dystrophin-glycoprotein complex (DGC). On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD.
    Bosnian journal of basic medical sciences / Udruzenje basicnih mediciniskih znanosti = Association of Basic Medical Sciences 03/2015; 15(2):42-9. DOI:10.17305/bjbms.2015.300 · 0.44 Impact Factor
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