Submissions for variant NM_005216.5(DDOST):c.1177G>A (p.Val393Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002629346	SCV003518686	uncertain significance	Congenital disorder of glycosylation type Ir	2024-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 410 of the DDOST protein (p.Val410Met). This variant is present in population databases (rs200636246, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DDOST-related conditions. ClinVar contains an entry for this variant (Variation ID: 2198382). 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%. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003992712	SCV004811216	uncertain significance	not provided	2024-03-01	criteria provided, single submitter	clinical testing	DDOST: PM2, PP3