Table 2 Databases commonly used in MTB

ClinVar

NCBI [https://www.ncbi.nlm.nih.gov/clinvar]

This database collects information on the diversity of the human genome and related diseases and provides it as a freely available archive. It contains polymorphism locations, gene names, and their relationship to diseases. Gene information is linked to dbSNP and dbVar at NCBI, and phenotypes are linked to MedGen. Information is also collected from the NIH Genetic Testing Registry (GTR), OMIM, and PubMed. Each data can be viewed in HTML format or downloaded in XML or tab-delimited format, and some data in VCF files.

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COSMIC

Wellcome Trust Sanger Institute [https://cancer.sanger.ac.uk/cosmic]

COSMIC is the most detailed and comprehensive resource for studying the effects of somatic mutations in human cancer. In addition to coding mutations, COSMIC covers all genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy number mutations, and drug resistance mutations. The core COSMIC database is complemented by additional datasets that allow users to contextualize the biomarkers they detect. The Cancer Gene Census provides a detailed catalog of > 700 genes involved in cancer, their biological functions, and descriptions of the genetic mechanisms that cause cancer. The Cancer Mutation Census provides information on the significance of all coding mutations based on biological and biochemical information from multiple sources. Mutation Actionability in Precision Oncology (Actionability) provides updates on drugs targeting specific somatic mutations at all stages of development. The Cell Lines Project advocates cell line omics data through systematic characterization of the genetics and genomics (variation and gene expression) of over 1,000 cancer cell lines.

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gnomAD

Broad Institute [https://gnomad.broadinstitute.org]

gnomAD is a resource developed by an international coalition of researchers with the goal of aggregating and harmonizing exome and genome data from various large-scale sequencing projects and making them available to a wider audience of scientists. The v2.1.1 dataset (GRCh37/hg19) provided by this site covers 125,748 exome sequences and 15,708 whole genome sequences of unrelated individuals sequenced as part of various disease-specific and population genetic studies (as of March 2022). v3.1.2 dataset (GRCh38) has 76,156 genomes selected (as of March 2022), similar to v2.

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OncoKB

Memorial Sloan Kettering Cancer Center [https://www.oncokb.org]

OncoKB is a groundbreaking precision oncology knowledge base that leverages the clinical expertise of Memorial Sloan Kettering (MSK) to provide accurate and up-to-date information on the biological and clinical significance of > 5,000 cancer gene mutations. On October 7, 2021, the U.S. Food and Drug Administration approved OncoKB for partial listing as the first tumor mutation database to be included in the Public Human Gene Mutation Database. This is the first tumor mutation database to be recognized by the FDA. Treatment information is categorized by the OncoKB Levels of Evidence system, which assigns clinical utility (from standard to investigational treatment) to individual mutational events.

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CIViC

The McDonnell Genome Institute at Washington University School of Medicine [https://civicdb.org/home]

CIViC is an expert knowledge base for the clinical interpretation of variants in cancer, describing the therapeutic, prognostic, diagnostic, and predispositional relevance of all types of genetic and somatic mutations. CIViC is committed to open source code, open access content, public application programming interfaces (APIs), and proof of supporting evidence, enabling the transparent creation of current and accurate variant interpretations for use in precision medicine for cancer.

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ClinicalTrials.gov

U.S. National Library of Medicine [https://www.clinicaltrials.gov]

ClinicalTrials.gov is a registry of clinical trials. Operated by the National Library of Medicine (NLM) of the U.S. National Institutes of Health, it is the largest clinical trials database with > 408,000 registered clinical trials in 220 countries. ClinicalTrials.gov was created as a result of the Food and Drug Administration Modernization Act of 1997 (FDAMA), which required the U.S. Department of Health and Human Services (HHS), through the NIH, to verify the effectiveness of experimental drugs for serious or life-threatening diseases and conditions by using the Clinical Trials. The NIH and the FDA jointly developed the site, which became available to the public in February 2000, to establish a registry of information on federal and private clinical trials conducted pursuant to an application.

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BRCA Exchange

Global Alliance for Genomics and Health [https://brcaexchange.org/]

This database aims to improve our understanding of the genetic basis of breast, ovarian, pancreatic, and other cancers by compiling BRCA1/2 gene mutations and corresponding clinical data from around the world. It is possible to search for BRCA1 or BRCA2 variants online.

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LOVD

Molecular Health [https://www.lovd.nl/]

The database provides a flexible and freely available tool to display gene-centric collections and DNA mutations. It also provides storage for patient-centric and NGS data, and extragenic mutations. LOVD is open source, released under the GPL license, and is being actively improved.

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