Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001319603 | SCV001510358 | uncertain significance | Congenital disorder of glycosylation type Ir | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 396 of the DDOST protein (p.Arg396Gln). This variant is present in population databases (rs74526704, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of DDOST-related conditions (PMID: 34462534). ClinVar contains an entry for this variant (Variation ID: 295076). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DDOST protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect DDOST function (PMID: 37848450). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV001319603 | SCV002520508 | pathogenic | Congenital disorder of glycosylation type Ir | 2022-05-19 | no assertion criteria provided | literature only |