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

dbSNP: rs1556300621

Total submissions: 5

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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001865690	SCV002305908	pathogenic	Charcot-Marie-Tooth Neuropathy X	2024-09-16	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). 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 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