Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000002392 | SCV003922969 | likely pathogenic | Glycogen storage disease, type V | 2023-03-14 | criteria provided, single submitter | clinical testing | Variant summary: PYGM c.1963G>A (p.Glu655Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251362 control chromosomes (gnomAD). c.1963G>A has been reported in the literature in individuals affected with Glycogen Storage Disease (example: Martinuzzi_1996, Yubero_2016, Joshi_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000002392 | SCV004207215 | likely pathogenic | Glycogen storage disease, type V | 2023-12-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000002392 | SCV004353768 | pathogenic | Glycogen storage disease, type V | 2024-07-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 655 of the PYGM protein (p.Glu655Lys). This variant is present in population databases (rs119103253, gnomAD 0.01%). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 8535454, 27243974; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as E654K. ClinVar contains an entry for this variant (Variation ID: 2302). 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. |
| Fulgent Genetics, |
RCV000002392 | SCV005684095 | likely pathogenic | Glycogen storage disease, type V | 2024-03-09 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000002392 | SCV000022550 | pathogenic | Glycogen storage disease, type V | 1995-01-01 | no assertion criteria provided | literature only |