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Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease‐associated variants, common sequence variants, and results from newborn screening
Author(s) -
Faria Douglas O. S.,
Groen Stijn L. M.,
HoogeveenWesterveld Marianne,
Niño Monica Y.,
Ploeg Ans T.,
Bergsma Atze J.,
Pijnappel W. W. M. Pim
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24148
Subject(s) - disease , missense mutation , biology , phenotype , clinical phenotype , in silico , genetics , genotype phenotype distinction , genetic variants , genotype , sequence database , gene , database , bioinformatics , medicine , computer science
Pompe disease is an inherited disorder caused by disease-associated variants in the acid α-glucosidase gene (GAA). The Pompe disease GAA variant database (http://www.pompevariantdatabase.nl) is a curated, open-source, disease-specific database, and lists disease-associated GAA variants, in silico predictions, and clinical phenotypes reported until 2016. Here, we provide an update to include 226 disease-associated variants that were published until 2020. We also listed 148 common GAA sequence variants that do not cause Pompe disease. GAA variants with unknown severity that were identified only in newborn screening programs were listed as a new feature to indicate the reason why phenotypes were still unknown. Expression studies were performed for common missense variants to predict their severity. The updated Pompe disease GAA variant database now includes 648 disease-associated variants, 26 variants from newborn screening, and 237 variants with unknown severity. Regular updates of the Pompe disease GAA variant database will be required to improve genetic counseling and the study of genotype-phenotype relationships.