Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000998845 | SCV001155147 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002236008 | SCV001542576 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 770 of the COL1A2 protein (p.Pro770Leu). This variant is present in population databases (rs149858889, gnomAD 0.02%). 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: 810133). 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. |
| Gene |
RCV000998845 | SCV002558194 | uncertain significance | not provided | 2022-07-18 | criteria provided, single submitter | clinical testing | Has not been previously published in association with COL1A2-related disorders to our knowledge; Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26264438) |
| Ambry Genetics | RCV002445154 | SCV002734278 | uncertain significance | Cardiovascular phenotype | 2022-12-28 | criteria provided, single submitter | clinical testing | The p.P770L variant (also known as c.2309C>T), located in coding exon 38 of the COL1A2 gene, results from a C to T substitution at nucleotide position 2309. The proline at codon 770 is replaced by leucine, 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. |
| Fulgent Genetics, |
RCV005047177 | SCV005669781 | 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 | 2024-05-07 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003943312 | SCV004764380 | uncertain significance | COL1A2-related disorder | 2024-01-08 | no assertion criteria provided | clinical testing | The COL1A2 c.2309C>T variant is predicted to result in the amino acid substitution p.Pro770Leu. This variant was reported as a no statistical significant variant (P value =0.0336) in a case control study of glioma risk (reported as rs149858889 in Table 3, Kinnersley. 2016. PubMed ID: 26264438). This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |