NM_000030.3(AGXT):c.697C>T (p.Arg233Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 11, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001070457.18

Allele description [Variation Report for NM_000030.3(AGXT):c.697C>T (p.Arg233Cys)]

NM_000030.3(AGXT):c.697C>T (p.Arg233Cys)

Gene:

AGXT:alanine--glyoxylate aminotransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.3

Genomic location:

Preferred name:

NM_000030.3(AGXT):c.697C>T (p.Arg233Cys)

HGVS:

NC_000002.12:g.240875125C>T
NG_008005.1:g.11381C>T
NM_000030.3:c.697C>TMANE SELECT
NP_000021.1:p.Arg233Cys
NP_000021.1:p.Arg233Cys
NC_000002.11:g.241814542C>T
NM_000030.2:c.697C>T
P21549:p.Arg233Cys

Protein change:

R233C; ARG233CYS

Links:

UniProtKB: P21549#VAR_008879; OMIM: 604285.0008; dbSNP: rs121908526

NCBI 1000 Genomes Browser:

rs121908526

Molecular consequence:

NM_000030.3:c.697C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Gene ID:118273509

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LOC113819684 [Penaeus vannamei]
Gene ID:113819684

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001235689	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 10862087, 17495019, 18282470, 18448374, 18782763, 9192270, 15849466, 17460142, 25629080, 28492532
SCV001873464	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001235689

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2024)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV001873464

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 10, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of 5 novel mutations in the AGXT gene.

Basmaison O, Rolland MO, Cochat P, Bozon D.

Hum Mutat. 2000 Jun;15(6):577.

PubMed [citation]

PMID:: 10862087

Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of patients with primary hyperoxaluria type 1.

Williams E, Rumsby G.

Clin Chem. 2007 Jul;53(7):1216-21. Epub 2007 May 10.

PubMed [citation]

PMID:: 17495019

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001235689.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 233 of the AGXT protein (p.Arg233Cys). This variant is present in population databases (rs121908526, gnomAD 0.04%). This missense change has been observed in individual(s) with primary hyperoxaluria type I (PMID: 9192270, 10862087, 17495019, 18282470, 25629080). ClinVar contains an entry for this variant (Variation ID: 5647). 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: 18448374, 18782763). This variant disrupts the p.Arg233 amino acid residue in AGXT. Other variant(s) that disrupt this residue have been observed in individuals with AGXT-related conditions (PMID: 9192270, 15849466, 17460142, 25629080), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001873464.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect by impairing protein level and in vitro acitivity for both the R233C major allele and the R233C minor allele with the P11L and I340M substitutions, although the in vitro activity and protein levels were lower for the R233C minor allele (Hopper et al., 2008); This variant is associated with the following publications: (PMID: 18782763, 9192270, 17495019, 10862087, 18448374, 20301460, 18282470, 24988064, 25629080, 33274618, 28906061, 31589614)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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