Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002234403 | SCV000752599 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1123 of the COL1A2 protein (p.Arg1123Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 526881). 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 with a negative 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. |
| Ce |
RCV001531679 | SCV001746919 | uncertain significance | not provided | 2021-06-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002457995 | SCV002616781 | uncertain significance | Cardiovascular phenotype | 2021-08-09 | criteria provided, single submitter | clinical testing | The p.R1123L variant (also known as c.3368G>T), located in coding exon 49 of the COL1A2 gene, results from a G to T substitution at nucleotide position 3368. The arginine at codon 1123 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001531679 | SCV002817782 | uncertain significance | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function |