ClinVar Miner

Submissions for variant NM_013328.4(PYCR2):c.596G>A (p.Arg199Gln)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003084854 SCV003483361 uncertain significance not provided 2022-05-18 criteria provided, single submitter clinical testing This variant disrupts the p.Arg199 amino acid residue in PYCR2. Other variant(s) that disrupt this residue have been observed in individuals with PYCR2-related conditions (PMID: 27130255, 30829456), which suggests that this may be a clinically significant amino acid residue. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This missense change has been observed in individual(s) with leukodystrophy (PMID: 30829456). This variant is present in population databases (rs376952965, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 199 of the PYCR2 protein (p.Arg199Gln).
GeneDx RCV003084854 SCV004169118 likely pathogenic not provided 2023-10-24 criteria provided, single submitter clinical testing Previously identified in the homozygous state in an individual with hypomyelinating leukodystrophy 10; however, this individual was also heterozygous for a variant in another gene that may have contributed to the phenotype (PMID: 30829456); 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: 37563452, 30829456)
Molecular Genetics laboratory, Necker Hospital RCV003084854 SCV004031281 pathogenic not provided 2021-11-08 no assertion criteria provided clinical testing

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