Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000119802 | SCV002236281 | pathogenic | PGM1-congenital disorder of glycosylation | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 263 of the PGM1 protein (p.Asp263Tyr). This variant is present in population databases (rs587777404, gnomAD 0.005%). This missense change has been observed in individual(s) with PGM1-congenital disorder of glycosylation (PMID: 24499211). ClinVar contains an entry for this variant (Variation ID: 133289). 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 PGM1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PGM1 function (PMID: 25288802). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003415904 | SCV004113754 | pathogenic | PGM1-related condition | 2023-03-01 | criteria provided, single submitter | clinical testing | The PGM1 c.787G>T variant is predicted to result in the amino acid substitution p.Asp263Tyr. This variant was reported in three patients with phosphoglucomutase deficiency, who were also compound heterozygotes for another pathogenic variant in the PGM1 gene. In all patients, phosphoglucomutase 1 enzyme activity was markedly diminished (Tegtmeyer et al 2014. PubMed ID: 24499211). Functional characterization showed that this variant leads to significant catalytic impairment (Lee Y et al 2014. PubMed ID: 25288802). Another pathogenic variant affecting this residue has been reported in patients with PGM1 deficiency (Tegtmeyer et al 2014. PubMed ID: 24499211). This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-64100604-G-T). This variant is interpreted as pathogenic. |
OMIM | RCV000119802 | SCV000154727 | pathogenic | PGM1-congenital disorder of glycosylation | 2014-02-06 | no assertion criteria provided | literature only |