Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001576561 | SCV001803773 | uncertain significance | not provided | 2023-07-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (HGMD) |
| Ambry Genetics | RCV002324150 | SCV002605917 | uncertain significance | Cardiovascular phenotype | 2022-03-28 | criteria provided, single submitter | clinical testing | The p.I1034V variant (also known as c.3100A>G), located in coding exon 46 of the COL1A2 gene, results from an A to G substitution at nucleotide position 3100. The isoleucine at codon 1034 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003771753 | SCV004594760 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-01-05 | 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: 1208292). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs746794922, gnomAD 0.03%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1034 of the COL1A2 protein (p.Ile1034Val). |