Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000815465 | SCV000955920 | pathogenic | Glycogen storage disease, type V | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 695 of the PYGM protein (p.Gly695Arg). This variant is present in population databases (rs768604948, gnomAD 0.004%). This missense change has been observed in individual(s) with McArdle disease (PMID: 16924035, 29143597, 30316539; externalcommunication). 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: 658611). 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 PYGM protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV000815465 | SCV001461271 | likely pathogenic | Glycogen storage disease, type V | 2020-09-16 | no assertion criteria provided | clinical testing |