 Help DocsTALITHA: daughter of the assemblyTALITHA provides a sortable, searchable interface to NCBI ClinVar data. ClinVar is a freely available public archive of records of the relationships between human variation and phenotypes, with supporting evidence. The database is maintained by the NCBI, and aggregates information about genomic variation and its relationship to human health. Currently as there is little consensus about how to describe the clinical condition that results from variation, there are often multiple Reference ClinVar Record accessions assigned to the same variant. It is anticipated that these will be merged by ClinVar staff over time as expert panels review the data and decide how to describe the phenotype. Meanwhile TALITHA has merged multiple ClinVar records for the same SNP for ease of use. Getting around in TALITHA From the 'Informatics' link on the main menu, hover over 'Queries' until a second menu list appears, then select TALITHA. You will then be presented with the default table, which shows 'everything' and is sorted by the 'Client' column. Like most data-driven apps in Opus 23 Pro, TALITHA uses a filterable/sortable table to display its data. At the bottom of the window is a jump table that allows you to move from one screen to the next. You can control how many rows to display by selecting an option from the 'Show' pull down menu. The default is 15. Filtering and sorting results The table will show results for the client's genotypes that have a positive match or 'no call' for ClinVar entries. Each of the six columns can be sorted in ascending or descending order by clicking on the column heading, and can be filtered by typing a search term in the search box. This can be a pathology or clinical condition, such as "Parkinson", "Cancer" or "Acetylator", an outcome such as "Risk factor" or "Protective", a SNP rs number, a gene, a genotype such as "TT", "AG", or any other text that appears in the table. The columns represent the following aspects of the ClinVar record: PATHOLOGY This column shows the possible outcome of the client having this SNP, but must be read in conjunction with the other columns. In autosomal recessive conditions the outcome may only manifest when the client has both risk alleles and if the clinical picture is pathogenic or risk factor. It is recommended to review these carefully and in light of the client's other known risk factors, lifestyle and environment. It may be important to be aware of the client's "carrier" status if they are heterozygous and may become a parent in the future, or that they may have passed a recessive SNP on to their offspring. Some entries in this field are "Not specified": some submissions to ClinVar are intended to report that a variant is benign with respect to a specific condition, which leaves the possibility that it is clinically relevant for a different condition. Other submissions want to report that the variant is generally benign, in that it does not appear to cause any genetic disorder that should be observable because it is highly penetrant. ClinVar has suggested that "not specified" is provided as the condition in submissions which are designed to indicate that they are not specifying any single condition, but rather that the variant is generally benign. Refer to ClinVar for more information. SNP The SNPs displayed in TALITHA may be rare, and as such may not necessarily be in the Opus 23 SNP database, but are collated from a comparison of the client's uploaded raw data and the ClinVar database. SNPs which do not have any data curated by Opus 23 editors have a pop-up which will display an aggregation of data from various sources. GENE Some of the ClinVar SNPs do not have genes associated with them: these may be intergenic, or the gene may not have been associated with the SNP at the time of the ClinVar submission. We recommend looking up the gene in 23andMe and/or dbSNP if necessary. Sometimes genomic locations may cover multiple overlapping genes, including those with shared exons, and so different sources may show a relationship with a different gene or genes. RISK This is the ClinVar risk allele for the specified pathology, or the protective allele where a mutation confers protection against a condition or disease. CLIENT This is the client's genotype as specified by the uploaded raw data. In some cases this may be "--", which designates a 'No call' in the client's raw data. In 23andMe this means a client's data may not allow determination of his or her genotype confidently at a particular SNP. The color of the box in this column is for ease of interpretation: red designates homozygous positive (or no call) for the 'risk' allele as listed by ClinVar, yellow designates heterozygous. CLINICAL This column represents the ClinVar interpretation of the effect of the risk genotype on the pathology. In some cases this is blank, in others it may contain an aggregation of several ClinVar entries. Refer to ClinVar for more information. |
