Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212241 | SCV001383820 | likely pathogenic | Osteogenesis imperfecta type I | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1441 of the COL1A1 protein (p.Asp1441Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL1A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 942286). 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 COL1A1 protein function with a positive predictive value of 95%. This variant disrupts the p.Asp1441 amino acid residue in COL1A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11826020, 19199251, 27509835). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Mayo Clinic Laboratories, |
RCV001508814 | SCV001715203 | uncertain significance | not provided | 2020-10-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003163610 | SCV003855110 | uncertain significance | Cardiovascular phenotype | 2022-12-21 | criteria provided, single submitter | clinical testing | The p.D1441N variant (also known as c.4321G>A), located in coding exon 51 of the COL1A1 gene, results from a G to A substitution at nucleotide position 4321. The aspartic acid at codon 1441 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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. |