Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002240325 | SCV001216447 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-06-23 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 848478). This missense change has been observed in individual(s) with COL1A2-related conditions (PMID: 21520333). This variant is present in population databases (rs41317144, gnomAD 0.04%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 528 of the COL1A2 protein (p.Asn528Ser). |
ARUP Laboratories, |
RCV001811631 | SCV001472209 | likely benign | not provided | 2019-09-21 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001811631 | SCV004035783 | uncertain significance | not provided | 2023-03-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign in association with a COL1A2-related disorder to our knowledge; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21520333, 18272325) |