Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Revvity Omics, |
RCV000186299 | SCV002021324 | likely pathogenic | Primary hyperoxaluria, type I | 2021-04-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003556222 | SCV004292183 | pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 112 of the AGXT protein (p.Ala112Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with primary hyperoxaluria type 1 (PMID: 12559847). ClinVar contains an entry for this variant (Variation ID: 204093). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects AGXT function (PMID: 12559847). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586609 | SCV005076440 | pathogenic | Primary hyperoxaluria | 2024-04-25 | criteria provided, single submitter | clinical testing | Variant summary: AGXT c.335C>A (p.Ala112Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 241646 control chromosomes (gnomAD). c.335C>A has been reported in the literature in individuals affected with Primary Hyperoxaluria Type 1 (Coulter-Mackie_2003). These data indicate that the variant is likely to be associated with disease. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated that the variant resulted in about ~2-5% of normal catalytic activity in both patient derived samples and in in vitro expression systems on the background of the major allele (Coulter-Mackie_2003, Coulter-Mackie_2006). The following publications have been ascertained in the context of this evaluation (PMID: 12559847, 16971151). ClinVar contains an entry for this variant (Variation ID: 204093). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Clinical Biochemistry Laboratory, |
RCV000186299 | SCV000239631 | pathogenic | Primary hyperoxaluria, type I | 2014-11-27 | no assertion criteria provided | in vitro |