Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000443040 | SCV000529859 | uncertain significance | not provided | 2017-11-28 | criteria provided, single submitter | clinical testing | The D1136G variant in the COL1A2 gene has been reported previously as a variant in a Ewings sarcoma-peripheral primitive neuroectodermal tumor, however it is unknown if it was a somatic variant or present in the germline (Crompton et al., 2014). The D1136G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D1136G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D1136G as a variant of uncertain significance. |
| Ambry Genetics | RCV002451023 | SCV002612730 | uncertain significance | Cardiovascular phenotype | 2019-06-11 | criteria provided, single submitter | clinical testing | The p.D1136G variant (also known as c.3407A>G), located in coding exon 49 of the COL1A2 gene, results from an A to G substitution at nucleotide position 3407. The aspartic acid at codon 1136 is replaced by glycine, an amino acid with similar 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. |
| Invitae | RCV002526333 | SCV003479219 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-08-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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: 387735). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL1A2 protein function. 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. This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1136 of the COL1A2 protein (p.Asp1136Gly). |