Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Myriad Genetics, |
RCV000186335 | SCV002060081 | uncertain significance | Primary hyperoxaluria, type I | 2021-10-20 | criteria provided, single submitter | clinical testing | NM_000030.2(AGXT):c.822G>C(E274D) is a missense variant classified as a variant of uncertain significance in the context of primary hyperoxaluria type 1. E274D has been observed in cases with relevant disease (PMID: 24988064). Functional assessments of this variant are available in the literature (PMID: 22923379, 24718375). E274D has been observed in population frequency databases (gnomAD: EAS 0.03%). In summary, there is insufficient evidence to classify NM_000030.2(AGXT):c.822G>C(E274D) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Labcorp Genetics |
RCV001852426 | SCV002299289 | uncertain significance | not provided | 2022-02-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 274 of the AGXT protein (p.Glu274Asp). This variant is present in population databases (rs146525143, gnomAD 0.03%). This missense change has been observed in individual(s) with primary hyperoxaluria (PMID: 19479957, 25629080). ClinVar contains an entry for this variant (Variation ID: 204129). 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 have shown that this missense change affects AGXT function (PMID: 24718375). 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. |
Fulgent Genetics, |
RCV000186335 | SCV002815658 | uncertain significance | Primary hyperoxaluria, type I | 2022-02-01 | criteria provided, single submitter | clinical testing | |
Rare Kidney Stone Consortium and the Mayo Clinic Hyperoxaluria Center, |
RCV000186335 | SCV004171790 | likely pathogenic | Primary hyperoxaluria, type I | 2023-10-27 | criteria provided, single submitter | clinical testing | ACMG:PS3 PS5 PM2 PP1 PP3 PP4 |
Clinical Biochemistry Laboratory, |
RCV000186335 | SCV000239681 | pathogenic | Primary hyperoxaluria, type I | 2014-11-27 | no assertion criteria provided | in vitro |