Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Biochemistry Laboratory, |
RCV000186253 | SCV000239577 | likely benign | Primary hyperoxaluria, type I | 2023-10-27 | criteria provided, single submitter | clinical testing | Enzyme has 75% normal activity in vitro (PMID:19479957). ACMG:PM2 BS3 BP4 |
Fulgent Genetics, |
RCV000186253 | SCV002790285 | uncertain significance | Primary hyperoxaluria, type I | 2021-08-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002517831 | SCV003459284 | uncertain significance | not provided | 2022-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 248 of the AGXT protein (p.Ala248Ser). This variant is present in population databases (rs180177260, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of primary hyperoxaluria type I (PMID: 19479957). ClinVar contains an entry for this variant (Variation ID: 204048). 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 AGXT protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on AGXT function (PMID: 19479957). 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. |