Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000990493 | SCV001141495 | pathogenic | Glycogen storage disease IXa1 | 2021-08-30 | criteria provided, single submitter | clinical testing | Pathogenic in haplotype with Met912Thr. Haplotype p.[Met912Thr; Ala929Pro] |
Invitae | RCV000990493 | SCV001395520 | uncertain significance | Glycogen storage disease IXa1 | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 912 of the PHKA2 protein (p.Met912Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 34093448). ClinVar contains an entry for this variant (Variation ID: 803727). 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 PHKA2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000990493 | SCV002512211 | uncertain significance | Glycogen storage disease IXa1 | 2021-05-31 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderate, PP3 supporting |