These databases are curated for nomenclature accuracy, duplicate entries and discrepancies in interpretation. The databases are supported by InSiGHT curators, who in turn are supported by panels of experts who review the pathogenicity assignments based on the broad experience of InSiGHT members and published information. Most of the databases are generally considered to present the most authoritative interpretation of the variants, based on defined criteria for interpretation. The data are published with the rider that they are for diagnostic use for individual families; any research use requires permission of the curator and relevant submitters.
The value of the databases is dependent on submission of information on variants. All interested in contributing are encouraged to contact the curator John-Paul Plazzer . Scientists of relevant disciplines (clinical, molecular and epidemiology) are welcome to join InSiGHT and its Variant Interpretation Committees (VIC).
The InSiGHT database includes classifications of pathogenicity for MMR variants with evidential basis. An explanation of the methodology can be found in Thompson BA, et al. Nat Genet 2014.
The InSiGHT database is recognised by the Human Variome Project and the Global Alliance for Genomic Health (GA4GH) as the world reference database for MMR gene variants, all data on all variants, whether benign, uncertain or pathogenic, are welcomed and should be submitted to the InSiGHT database (prior registration required) or via the curator John-Paul Plazzer. The InSiGHT VIC provides interpretation of all variants, whether new to the database or those for which extra data are available. The InSiGHT VIC works closely with the European MMR cDNA Working Group, which is able to help in the analysis of variants suspected of causing splicing defects.