Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001508219 | SCV000573481 | uncertain significance | not provided | 2022-01-04 | 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 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); This variant is associated with the following publications: (PMID: 24077912, 26582918) |
Invitae | RCV002230957 | SCV000627329 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 96 of the COL1A2 protein (p.Met96Val). This variant is present in population databases (rs763509640, gnomAD 0.008%). 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: 423747). 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 95%. 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. |
Center for Human Genetics, |
RCV000659367 | SCV000781178 | uncertain significance | Connective tissue disorder | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002475951 | SCV000895869 | uncertain significance | Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, cardiac valvular type; Osteoporosis; Ehlers-danlos syndrome, arthrochalasia type, 2; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 | 2021-11-02 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001508219 | SCV001714222 | uncertain significance | not provided | 2022-06-15 | criteria provided, single submitter | clinical testing | BS1 |
Ambry Genetics | RCV002438185 | SCV002745911 | uncertain significance | Cardiovascular phenotype | 2022-02-16 | criteria provided, single submitter | clinical testing | The p.M96V variant (also known as c.286A>G), located in coding exon 7 of the COL1A2 gene, results from an A to G substitution at nucleotide position 286. The methionine at codon 96 is replaced by valine, an amino acid with highly similar properties. This amino acid position is 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. |