Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672270 | SCV000797361 | uncertain significance | PMM2-congenital disorder of glycosylation | 2018-01-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000672270 | SCV003443485 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 206 of the PMM2 protein (p.Phe206Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital disorder of glycosylation type 1a (PMID: 19165618). 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: 556280). 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. This variant disrupts the p.Phe206 amino acid residue in PMM2. Other variant(s) that disrupt this residue have been observed in individuals with PMM2-related conditions (PMID: 12357336), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |