Clinical Domain Working Groups

Our main goal is to curate variants in genes associated with metabolic diseases primarily involving the lysosome, with an emphasis on disorders on the Recommended Universal Screening Panel (RUSP). Initially, we focused the VCEP’s efforts on modification of the ACMG-AMP criteria for interpretation of variants within GAA.  Deficiency of acid alpha-glucosidase, encoded by GAA, causes Pompe disease (OMIM 232300) glycogen storage disease type II; acid maltase deficiency). This expert panel has also completed specifications for IDUA and is actively curating variants within IDUA. Deficiency of alpha-L-iduronidase, encoded by IDUA, causes Mucopolysaccharidosis Type 1 (MPS I : OMIM 607014, 607015, 607016). Variant interpretation for both genes is an important component of diagnostic confirmation for symptomatic patients, guidance and interpretation for individual identified through newborn screening, as well as individuals identified through genomic sequencing pipelines. The VCEP members will collectively decide which gene to develop specifications for next.

Please note, in February 2023 the Lysosomal Diseases VCEP was renamed from Lysosomal Storage Disorders VCEP.