Submissions for variant NM_000030.3(AGXT):c.568G>A (p.Gly190Arg)

gnomAD frequency: 0.00004  dbSNP: rs180177239

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169439	SCV000220856	likely pathogenic	Primary hyperoxaluria, type I	2014-11-06	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV000816747	SCV000957270	pathogenic	not provided	2023-10-11	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 190 of the AGXT protein (p.Gly190Arg). This variant is present in population databases (rs180177239, gnomAD 0.01%). This missense change has been observed in individuals with primary hyperoxaluria (PMID: 9604803, 15849466, 15961946, 27568336, 27935012). It has also been observed to segregate with disease in related individuals. This variant is also known as c.690G>A. ClinVar contains an entry for this variant (Variation ID: 189047). 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. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000169439	SCV001752663	pathogenic	Primary hyperoxaluria, type I	2021-06-30	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000169439	SCV003809004	pathogenic	Primary hyperoxaluria, type I	2022-09-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000816747	SCV003845926	pathogenic	not provided	2022-09-25	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27935012, 27568336, 18282470, 15849466, 31589614, 24988064, 23810941, 30341509, 10541294, 25629080, 19571789, 17460142, 9604803)
Baylor Genetics	RCV000169439	SCV004196492	pathogenic	Primary hyperoxaluria, type I	2024-01-28	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV000169439	SCV005382428	pathogenic	Primary hyperoxaluria, type I	2023-05-20	criteria provided, single submitter	clinical testing	The observed missense c.568G>A (p.Gly190Arg) variant in AGXT gene has been reported in both homozygous and compound heterozygous states in multiple individuals affected with Primary Hyperoxaluria (Frishberg et al., 2005; Nagara et al., 2013; M'dimegh et al., 2016; M'dimegh et al., 2017). It has also been observed to segregate with disease in related individuals (Nagara et al., 2013; M'dimegh et al., 2017). This variant is present with allele frequency of 0.004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic/ Pathogenic (multiple submissions). Multiple lines of computational evidence (Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease Causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid of p.Gly190Arg in AGXT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 190 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic.
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000169439	SCV000239656	pathogenic	Primary hyperoxaluria, type I	2014-11-27	no assertion criteria provided	in vitro
Natera, Inc.	RCV000169439	SCV002076464	pathogenic	Primary hyperoxaluria, type I	2020-10-05	no assertion criteria provided	clinical testing