NOTE:
These data are for research purposes only. While the ClinGen data are
open to the public, users seeking information about a personal medical or
genetic condition are urged to consult with a qualified physician for
diagnosis and for answers to personal medical questions.
UCSC presents these data for use by qualified professionals, and even such professionals should use caution in interpreting the significance of information found here. No single data point should be taken at face value and such data should always be used in conjunction with as much corroborating data as possible. No treatment protocols should be developed or patient advice given on the basis of these data without careful consideration of all possible sources of information.
No attempt to identify individual patients should be undertaken. No one is authorized to attempt to identify patients by any means.
The ClinGen Dosage Sensitivity dataset shows evidence supporting or refuting haploinsufficiency (loss) and triplosensitivity (gain) as mechanisms for disease at gene-level and larger genomic regions.
A rating system is used to classify the evidence supporting or refuting dosage sensitivity for individual genes and regions, which takes in consideration the following criteria: number of causative mutations reported, patterns of inheritance, consistency of phenotype, evidence from large-scale case-control studies, mutational mechanisms, data from public genome variation databases, and expert consensus opinion.
The system is intended to be of a "dynamic nature", with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected is displayed within a publicly available database. Evidence that haploinsufficiency or triplosensitivity of a gene is associated with a specific phenotype will aid in the interpretive assessment of CNVs including that gene.
There are two subtracks in this track set:
Scores are used to classify the evidence of the supporting dosage sensitivity map:
For more information on the use of the scores see the ClinGen FAQs. Items are shaded according to dosage sensitivity type. red for haploinsufficiency, blue for triplosensitivity, violet for associations with autosomal recessive phenotypes, and grey for genes/regions that have not been evaluated yet or no evidence is available. A light to dark gradient color is used according to the degree of supporting evidence.
Mouseover on items shows the supporting evidence of dosage sensitivity and respective scores. All tracks can be filtered according to the supporting evidence of dosage sensitivity.
The raw data can be explored interactively with the Table Browser, or the Data Integrator. For automated analysis, the data may be queried from our REST API. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information.
Thank you to ClinGen and NCBI, especially Erin Rooney Riggs for technical coordination and consultation, and to Christopher Lee, Anna Benet-Pages, and Maximilian Haeussler of the Genome Browser team for engineering the track display.
Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, Ledbetter DH, Maglott DR, Martin CL, Nussbaum RL et al. ClinGen--the Clinical Genome Resource. N Engl J Med. 2015 Jun 4;372(23):2235-42. PMID: 26014595; PMC: PMC4474187
Riggs ER, Church DM, Hanson K, Horner VL, Kaminsky EB, Kuhn RM, Wain KE, Williams ES, Aradhya S, Kearney HM et al. Towards an evidence-based process for the clinical interpretation of copy number variation. Clin Genet. 2012 May;81(5):403-12. PMID: 22097934; PMC: PMC5008023
Strande NT, Riggs ER, Buchanan AH, Ceyhan-Birsoy O, DiStefano M, Dwight SS, Goldstein J, Ghosh R, Seifert BA, Sneddon TP et al. Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource. Am J Hum Genet. 2017 Jun 1;100(6):895-906. PMID: 28552198; PMC: PMC5473734