title: 'A variant of uncertain significance' and the proliferation of human disease gene databases.
abstract: The rapid accumulation of mutation data has led to the creation of nearly 300 locus-specific mutation databases. These sites may contain a few dozen to almost 20,000 mutations for a given gene. Many of the mutations are uncharacterised and have no known effects on the gene product, the 'variant of uncertain significance'. Here, the statistics of mutation distribution are examined for six different gene databases: BRCA1 and BRCA2, haemoglobin-beta (HBB), HPRT1, CFTR and TP53. The percentage of all possible point mutations for a protein (the mutation space) is calculated for each gene and the question 'How much mutation data is enough?' is raised.
authors.affiliation: Department of Molecular Sciences and The UT Center of Excellence in Genomics and Bioinformatics, University of Tennessee, Memphis, TN 38163, USA. dnelson@utmem.edu
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
mesh_terms: D030541:Databases, Genetic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016158:Genes, p53; D014644:Genetic Variation; D005826:Genetics, Medical; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009152:Mutagenicity Tests; D009154:Mutation
chemical_list: D006454:Hemoglobins; C020622:hemoglobin B; D007041:Hypoxanthine Phosphoribosyltransferase