Content of the database
This database contains information about the pathogenic variants which are reported in papers indexed in PubMed for the SMOC1 gene and the related mendelian disease microphthalmia with limb anomalies.
In the SMOC1 homepage you can find:
- a link to a revised list of the most common features of the disorder. In this list percentage, number of patients who show the clinical sign, type of clinical sign and its HPO terms are reported.
- statistics about the entries represented in the database, among them you can find the most common pathogenic variant for the disorder with its estimated frequency in general population.
- a list of the reported pathogenic variants. You can access to related pathogenic variant page by clicking on its corresponding “GO!” link.
In each variant page we report general information on location, frequency, revised interpretation and the references. Furthermore, we report the number of patients, their clinical signs with HPO terms and their familial pedigree.
About the SMOC1 clinical signs list
The clinical list is composed by a list of clinical signs. For each clinical signs you have the percentage in the affected individuals and the related HPO ID primary number. Similar clinical signs can be grouped up to three different levels of classification. The higher level is always a superclass of the related lower levels. A lower level is always a subclass of a related higher level.
The name of the clinical signs, as well as the superclasses and subclasses, are defined according to the terms and the tree structure from Human Phenotype Ontology (HPO). Here below you can find a shot of a clinical list which shows the three aforementioned levels.
|synostosis involving the 4th metacarpal
The first level is the entries which is dysplayed in bold. The second level are the entries which are displayed in smaller fonts. The third level are the entries which are displayed with fonts of the same size of the second level, but with an indent from the left and right margins of the table.
The distance between the superclass and the subclass can be variable, even if we try not to include distance higher than three nodes. However, the distance is a factor which is evaluated in a manual way. As general rule, the curators of the database try to minimize this distance in order not to give too much relevance to clinical signs which are actually peripheral.
For example, in the SMOC1 gene homepage many clinical signs for abnormality of the face are reported as isolated entities (first level of classification only) with a low percentage of representation (5.56%, 1/18). If we had procedeed to group all these clinical signs inside the superclass of “abnormality of the face”, these clinical signs would have been overrepresented in the clinical list and ranked higher than more relevant clinical sign. Furthermore, it is possible to run into a possibility of multiple choice for grouping similar clinical signs. In all these cases we will proceed according to the information available from the literature and medical experience. This evaluation is not automated yet and it is manually applied and it is an interpretation of our scientists. We also try to keep the three levels-structure and not to expand the tree-structure with additional sub-levels.
Please, note that the number of patients included in a level description may be or not may be the sum of the patients included in the related second level classificiation. That depends on the simultanepus presence of different but similar clinical signs in the same patient.
The information about the number of the patients for a clinical sign is strictly connected to how many individuals are affected by the clinical sign reported in that same level, without considering other clinical signs that are included in the same superclass and that can be present in the same individual. For example, if two patients out of 20 show 2-3 toe cutaneous syndactyly at the right foot and 3-5 toe syndactyly at the left foot, they will be both reported in a second level with their percentage (10%, 2/20), but in the superclass of toe syndactyly (reported in the first level) the percentage will be still 10%, 2/20, because these two entries coexist in two individuals out of 20.
General population databases consulted
ExAC. Exome Aggregation Consortium. It is a coalition of investigators seeking to aggregate and harmonize exome sequencing data from a wide variety of large-scale sequencing projects, and to make summary data available for the wider scientific community. The data set provided on this website spans 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies.
ESP. NHLBI Exome Sequencing Project. The goal of this project is to discover novel genes and mechanisms contributing to heart, lung and blood disorders by pioneering the application of next-generation sequencing of the protein coding regions of the human genome across diverse, richly-phenotyped populations and to share these datasets and findings with the scientific community to extend and enrich the diagnosis, management and treatment of heart, lung and blood disorders.
1000GP. 1000 Genomes Project ran between 2008 and 2015, creating the largest public catalogue of human variation and genotype data. As the project ended, the Data Coordination Centre at EMBL-EBI has received continued funding from the Wellcome Trust to maintain and expand the resource.
The information reported in this database is based exclusively on current literature. We cannot garantuee that the content is updated everytime. The information is provided exclusively only for research purposes and the authors of these reviews are not responsible if the reported information is used for clinical diagnostics purposes.
Relevant tools for building this database are:
PubMed from NCBI: https://www.ncbi.nlm.nih.gov/pubmed
Human Phenotype Ontology: http://human-phenotype-ontology.github.io
Genial Pedigree: http://www.pedigreedraw.com