Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Morava/Kozicz Lab, |
RCV002261482 | SCV002540746 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2022-07-05 | criteria provided, single submitter | clinical testing | The variant c.728T>C (p.Leu243Pro) is a missense substitution in exon 8 of8 that results in the alteration of the codon at amino acid position 243. The variant has not been listed in gnomAD or dbSNP. This variant has been previously reported as a disease-causing mutation by the Human Gene Mutation Database (HGMD, CM055486) with association with PMM2-CDG. In addition, the variant has been reported by Haeuptle et al, 2009 in a patient with CDG. |
| Labcorp Genetics |
RCV002261482 | SCV003443487 | pathogenic | PMM2-congenital disorder of glycosylation | 2024-04-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 243 of the PMM2 protein (p.Leu243Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PMM2-congenital disorder of glycosylation (CDG-Ia) (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1693586). 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%. For these reasons, this variant has been classified as Pathogenic. |