Submission Details

STT3A was first reported in relation to autosomal dominant congenital disorder of glycosylation, type Iw in 2021 (Wilson et al., PMID 34653363). At least nine variants (missense) that have been reported in 11 probands in 3 publications (PMIDs 34653363, 39891251, 39435313) are included in this curation. Patients have a range of symptoms, including developmental delay, intellectual disability, skeletal anomalies, short stature, macrocephaly, dysmorphic features, and muscle cramps. 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 recessive 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 34653363, 19167329) as well as a zebrafish model (PMID 39891251). In summary, there is definitive evidence to support the relationship between STT3A and autosomal dominant congenital disorder of glycosylation, type Iw. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date June 5, 2025 (SOP Version 11).