Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522211 | SCV000621310 | uncertain significance | not provided | 2017-10-06 | criteria provided, single submitter | clinical testing | The I899T variant in the COL1A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I899T variant is not observed in large population cohorts (Lek et al., 2016). The I899T 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 not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I899T as a variant of uncertain significance. |
| Invitae | RCV001853683 | SCV002119835 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2022-07-12 | 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: 452498). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 899 of the COL1A2 protein (p.Ile899Thr). |
| Ambry Genetics | RCV002438260 | SCV002745351 | uncertain significance | Cardiovascular phenotype | 2019-10-02 | criteria provided, single submitter | clinical testing | The p.I899T variant (also known as c.2696T>C), located in coding exon 42 of the COL1A2 gene, results from a T to C substitution at nucleotide position 2696. The isoleucine at codon 899 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |