ClinVar Miner

Submissions for variant NM_006907.4(PYCR1):c.356G>A (p.Arg119His)

gnomAD frequency: 0.00001  dbSNP: rs121918377
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University RCV000761519 SCV000891650 pathogenic PYCR1-related de Barsy syndrome 2017-12-30 criteria provided, single submitter curation
Baylor Genetics RCV000014084 SCV001525292 pathogenic Autosomal recessive cutis laxa type 2B 2020-01-20 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001543486 SCV001762086 likely pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
GeneDx RCV001543486 SCV003930944 pathogenic not provided 2023-06-05 criteria provided, single submitter clinical testing Functional studies using recombinant protein expressed and purified in E.coli showed negligible enzyme activity (Li et al., 2017); 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: 18348262, 19648921, 30450527, 28194412)
Labcorp Genetics (formerly Invitae), Labcorp RCV001543486 SCV005837783 likely pathogenic not provided 2024-08-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 119 of the PYCR1 protein (p.Arg119His). This variant is present in population databases (rs121918377, gnomAD 0.007%). This missense change has been observed in individuals with autosomal recessive cutis laxa (PMID: 19648921, 23963297, 30450527). ClinVar contains an entry for this variant (Variation ID: 13197). 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 PYCR1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PYCR1 function (PMID: 28194412). This variant disrupts the p.Arg119 amino acid residue in PYCR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23963297, 24035636, 25865492, 30450527). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000014084 SCV000034332 pathogenic Autosomal recessive cutis laxa type 2B 2009-09-01 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV001291133 SCV001479509 likely pathogenic Wiedemann-Rautenstrauch-like progeroid syndrome no assertion criteria provided research

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