Submission Details

STT3A was first reported in relation to autosomal recessive STT3A-congenital disorder of glycosylation (CDG type 1w) in 2013 (Shrimal et al., PMID 23842455). Two variants (missense) that have been reported in 3 probands in 3 publications (PMIDs 23842455, 28424003, 30701557) are included in this curation. Patients have a range of symptoms, including developmental delay, intellectual disability, failure to thrive, hypotonia and seizures. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Variants in STT3A have been reported in individuals with the following disease entities: autosomal dominant congenital disorder of glycosylation, type Iw (MIM: 619714) and autosomal recessive congenital disorder of glycosylation, type Iw (MIM: 615596). Per criteria outlined by the ClinGen Lumping and Splitting guidelines, the curation for autosomal dominant congenital disorder of glycosylation, type 1w has been curated separately. This gene-disease relationship is supported by in vitro and in vivo assays showing a defect in N-linked glycosylation (PMIDs 23842455, 30701557, 19167329) as well as a zebrafish model (PMID 39891251). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date April 16, 2025 (SOP Version 11).