Rare Disease Variants ID'd in Literature Not Always Found in Accessible Databases

Nearly a quarter of variants reported to be pathogenic for X-linked Creatine Transporter Deficiency in articles available in PubMed are not present in public variant databases, according to a new analysis in BMC Genomics. Researchers from the US National Institutes of Health and the Frederick National Laboratory for Cancer Research sifted through the literature to identify 185 unique variants in SLC6A8, the gene affected in X-linked Creatine Transporter Deficiency. The researchers further determined the variants' pathogenicity based on American College of Medical Genetics and Genomics guidelines and searched to see whether the variants were present in databases or datasets like ClinVar, dbSNP, gnomAD, and 1,000 Genomes. Overall, 24 percent of pathogenic variants for X-linked Creatine Transporter Deficiency were not found in an open-access database, a finding the researchers say is likely not restricted to this one disease. "Despite being published in the literature, pathogenicity data on patient variants may remain inaccessible for genetic diagnosis, therapeutic target identification, mechanistic understanding, or hypothesis generation," the researchers write.