ClinVar Miner

Submissions for variant NM_002764.4(PRPS1):c.640C>T (p.Arg214Trp)

dbSNP: rs1556300621
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075877 SCV001241518 likely pathogenic Retinal dystrophy 2019-08-15 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196872 SCV001367506 likely pathogenic Phosphoribosylpyrophosphate synthetase superactivity 2020-01-20 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP2,PP3.
Invitae RCV001865690 SCV002305908 pathogenic Charcot-Marie-Tooth Neuropathy X 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 214 of the PRPS1 protein (p.Arg214Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of PRPS1-related conditions (PMID: 28967191). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 446163). 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 PRPS1 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg214 amino acid residue in PRPS1. Other variant(s) that disrupt this residue have been observed in individuals with PRPS1-related conditions (PMID: 28967191), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Hardcastle Lab, UCL Institute of Ophthalmology RCV000590916 SCV000611156 likely pathogenic Retinal dystrophy; Hearing loss 2017-01-01 no assertion criteria provided research
Genomics England Pilot Project, Genomics England RCV001542719 SCV001760498 likely pathogenic Arts syndrome no assertion criteria provided clinical testing

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