Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001546731 | SCV001766303 | pathogenic | not provided | 2022-10-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34703884) |
Institute of Human Genetics, |
RCV001780406 | SCV002026403 | uncertain significance | Glycosylphosphatidylinositol biosynthesis defect 15 | 2021-10-11 | criteria provided, single submitter | clinical testing | This variant was identified as compound heterozygous with NM_003801.4:c.1477_1478del._x000D_ Criteria applied: PM3, PS4_SUP, PM2_SUP, PP3 |
Invitae | RCV001546731 | SCV002222616 | uncertain significance | not provided | 2023-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 50 of the GPAA1 protein (p.Met50Lys). This variant is present in population databases (rs200581623, gnomAD 0.005%). This missense change has been observed in individual(s) with congenital disorder of glycosylation (GPAA1-CDG) (PMID: 34703884). 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: 1187326). 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 GPAA1 protein function. 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. |
Ce |
RCV001546731 | SCV002564027 | likely pathogenic | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | GPAA1: PM3:Strong, PM2 |