Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001857589 | SCV002247417 | pathogenic | not provided | 2023-04-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 204118). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser205 amino acid residue in AGXT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2039493; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects AGXT function (PMID: 19479957). 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. This missense change has been observed in individuals with primary hyperoxaluria type 1 (PMID: 27935012, 30541997, 32556641). This variant is present in population databases (rs180177248, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 205 of the AGXT protein (p.Ser205Leu). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307437 | SCV002600425 | pathogenic | Primary hyperoxaluria | 2022-10-11 | criteria provided, single submitter | clinical testing | Variant summary: AGXT c.614C>T (p.Ser205Leu) results in a non-conservative amino acid change located in the Aminotransferase class V domain (IPR000192) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251126 control chromosomes. c.614C>T has been reported in the literature as homozygous and compound heterozygous genotypes in individuals affected with Primary Hyperoxaluria Type 1 (example, Li_2018, Birtel_2019, Chen_2021, Zhao_2020). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Williams_2009). The most pronounced variant effect results in <3% of normal alanine:glyoxylate aminotransferase (AGT) activity in vitro. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000186324 | SCV004192772 | pathogenic | Primary hyperoxaluria, type I | 2023-02-21 | criteria provided, single submitter | clinical testing | |
Clinical Biochemistry Laboratory, |
RCV000186324 | SCV000239664 | pathogenic | Primary hyperoxaluria, type I | 2014-11-27 | no assertion criteria provided | in vitro |