Submissions for variant NM_000030.3(AGXT):c.1049G>A (p.Gly350Asp)

dbSNP: rs180177156

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169365	SCV000220737	likely pathogenic	Primary hyperoxaluria, type I	2014-09-25	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV001067841	SCV001232922	pathogenic	not provided	2023-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 350 of the AGXT protein (p.Gly350Asp). This variant is present in population databases (rs180177156, gnomAD 0.03%). This missense change has been observed in individual(s) with hyperoxaluria (PMID: 9604803, 23551880, 30341509, 35149915). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G1171A. ClinVar contains an entry for this variant (Variation ID: 188986). 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: 22018727, 22923379, 30341509). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV000169365	SCV002073273	likely pathogenic	Primary hyperoxaluria, type I		criteria provided, single submitter	clinical testing	The missense variant p.G350D in AGXT (NM_000030.3) has been reported previously in multiple affected indviduals (Du DF et al; Rao NM et al). The variant was submitted to ClinVar as Likely Pathogenic. The p.G350D variant is observed in 11/30,610 (0.0359%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between glycine and aspartic acid. The p.G350D missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 350 of AGXT is conserved in all mammalian species. The nucleotide c.1049 in AGXT is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000169365	SCV002809820	likely pathogenic	Primary hyperoxaluria, type I	2021-10-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000169365	SCV004192231	pathogenic	Primary hyperoxaluria, type I	2024-01-03	criteria provided, single submitter	clinical testing
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000169365	SCV000239699	pathogenic	Primary hyperoxaluria, type I	2014-11-27	no assertion criteria provided	in vitro
Sydney Genome Diagnostics, Children's Hospital Westmead	RCV001328117	SCV001449178	pathogenic	Primary hyperoxaluria	2018-10-24	no assertion criteria provided	clinical testing	This patient is homozygous for a known pathogenic variant, c.1049G>A p.(Gly350Asp), in the AGXT gene. This variant (dbSNP: rs180177156) has been previously reported in the homozygote form in a patient with primary hyperoxaluria type I (Rao et al 2014 J Neuroimaging 24:411-3).
Chinese Inherited Urolithiasis Consortium, The Affiliated Yantai Yuhuangding Hospital of Qingdao University	RCV000169365	SCV005368586	likely pathogenic	Primary hyperoxaluria, type I	2024-08-26	no assertion criteria provided	clinical testing	Variant_type:missense/MutationTaster:Disease_causing_automatic/CADD:Damaging/phyloP:Conserved/phastCons:Conserved/gnomAD_exome_EastAsian:0/ExAC_EastAsian:0/dbSNP:rs180177156