ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.52A>C (p.Thr18Pro)

gnomAD frequency: 0.00001  dbSNP: rs757040733
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822111 SCV000962897 likely pathogenic PMM2-congenital disorder of glycosylation 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 18 of the PMM2 protein (p.Thr18Pro). This variant is present in population databases (rs757040733, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PMM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 664093). 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 PMM2 protein function with a positive predictive value of 95%. This variant disrupts the p.Thr18 amino acid residue in PMM2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15844218, 16435227, 28139241). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282385 SCV002571899 uncertain significance not specified 2022-08-09 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000822111 SCV002783529 uncertain significance PMM2-congenital disorder of glycosylation 2022-04-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV000822111 SCV002089460 uncertain significance PMM2-congenital disorder of glycosylation 2020-10-12 no assertion criteria provided clinical testing

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.