ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.781C>A (p.Pro261Thr)

gnomAD frequency: 0.00002  dbSNP: rs141075408
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002233538 SCV000819702 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 261 of the COL1A2 protein (p.Pro261Thr). This variant is present in population databases (rs141075408, gnomAD 0.003%). 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: 570914). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL1A2 protein function. 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.
GeneDx RCV002473111 SCV002770269 uncertain significance not provided 2022-06-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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); Has not been previously published as pathogenic or benign to our knowledge

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.