ClinVar Miner

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

gnomAD frequency: 0.00005  dbSNP: rs121908526
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000006001 SCV000790193 likely pathogenic Primary hyperoxaluria, type I 2017-03-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000006001 SCV001162945 pathogenic Primary hyperoxaluria, type I criteria provided, single submitter clinical testing
Invitae RCV001070457 SCV001235689 pathogenic not provided 2021-12-17 criteria provided, single submitter clinical testing 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. 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.
GeneDx RCV001070457 SCV001873464 pathogenic not provided 2021-02-25 criteria provided, single submitter clinical testing 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); 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: 9192270, 18782763, 28906061, 31589614, 33274618, 25629080, 24988064, 18282470, 17495019, 20301460, 18448374, 10862087)
Myriad Women's Health, Inc. RCV000006001 SCV002060387 likely pathogenic Primary hyperoxaluria, type I 2021-11-03 criteria provided, single submitter clinical testing NM_000030.2(AGXT):c.697C>T(R233C) is a missense variant classified as likely pathogenic in the context of primary hyperoxaluria type 1. R233C has been observed in cases with relevant disease (PMID: 10862087, 18282470, 25629080). Functional assessments of this variant are available in the literature (PMID: 18782763, 17495019, 18448374). Internal structural analysis of the variant is supportive of pathogenicity. R233C has been observed in population frequency databases (gnomAD: AFR 0.04%). In summary, NM_000030.2(AGXT):c.697C>T(R233C) is a missense variant that has internal structural support for pathogenicity and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000006001 SCV000026183 pathogenic Primary hyperoxaluria, type I 1997-06-01 no assertion criteria provided literature only
GeneReviews RCV000006001 SCV000172456 pathogenic Primary hyperoxaluria, type I 2014-07-17 no assertion criteria provided literature only
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000006001 SCV000239670 pathogenic Primary hyperoxaluria, type I 2014-11-27 no assertion criteria provided in vitro
Natera, Inc. RCV000006001 SCV001456050 pathogenic Primary hyperoxaluria, type I 2020-09-16 no assertion criteria provided clinical testing

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