Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002034952 | SCV002111007 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2021-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1289 of the COL1A2 protein (p.Ala1289Pro). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 expected to disrupt COL1A2 protein function. This missense change has been observed in individual(s) with clinical features of autosomal dominant COL1A2-related conditions (Invitae). It has also been observed to segregate with disease in related individuals. |
| Ambry Genetics | RCV004996024 | SCV005561465 | uncertain significance | Cardiovascular phenotype | 2024-09-20 | criteria provided, single submitter | clinical testing | The c.3865G>C (p.A1289P) alteration is located in exon 51 (coding exon 51) of the COL1A2 gene. This alteration results from a G to C substitution at nucleotide position 3865, causing the alanine (A) at amino acid position 1289 to be replaced by a proline (P). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |