Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001957511 | SCV002206401 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2021-09-21 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs368702549, ExAC 0.003%). This sequence change replaces arginine with histidine at codon 405 of the COL1A2 protein (p.Arg405His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. |
| Gene |
RCV002254973 | SCV002526278 | uncertain significance | not provided | 2023-03-29 | criteria provided, single submitter | clinical testing | 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 has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002352595 | SCV002660467 | uncertain significance | Cardiovascular phenotype | 2020-04-22 | criteria provided, single submitter | clinical testing | The p.R405H variant (also known as c.1214G>A), located in coding exon 22 of the COL1A2 gene, results from a G to A substitution at nucleotide position 1214. The arginine at codon 405 is replaced by histidine, an amino acid with highly 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. |