ClinVar Miner

Submissions for variant NM_000030.3(AGXT):c.1151T>C (p.Leu384Pro)

gnomAD frequency: 0.00001  dbSNP: rs180177165
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002516975 SCV003525306 uncertain significance not provided 2024-09-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 384 of the AGXT protein (p.Leu384Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hyperoxaluria (PMID: 19479957). ClinVar contains an entry for this variant (Variation ID: 204150). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt AGXT protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV000186357 SCV005059314 likely pathogenic Primary hyperoxaluria, type I 2024-02-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005237680 SCV005887299 uncertain significance not specified 2025-01-14 criteria provided, single submitter clinical testing Variant summary: AGXT c.1151T>C (p.Leu384Pro) 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 allele was found at a frequency of 9.2e-06 in 217048 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1151T>C has been reported in the literature in individual(s) affected with Primary Hyperoxaluria Type 1 but clinical presentations and genotypes have not been provided (Williams_2009). These report(s) do not provide unequivocal conclusions about association of the variant with Primary Hyperoxaluria Type 1. At least one publication reports experimental evidence evaluating an impact on protein function and showed significantly reduced activity and stability; however, these data does not allow convincing conclusions about the variant effect (Lage_2014). ClinVar contains an entry for this variant (Variation ID: 204150). Based on the evidence outlined above, the variant was classified as uncertain significance.
Clinical Biochemistry Laboratory, Health Services Laboratory RCV000186357 SCV000239704 pathogenic Primary hyperoxaluria, type I 2014-11-27 no assertion criteria provided in vitro

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