ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*3701C>T (rs147826200)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199244 SCV000255226 uncertain significance Charcot-Marie-Tooth disease type 4 2018-01-23 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1166 of the PRX protein (p.Pro1166Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant has not been reported in the literature in individuals with PRX-related disease. ClinVar contains an entry for this variant (Variation ID: 216835). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202796 SCV000258270 uncertain significance not specified 2015-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000202796 SCV000515632 likely benign not specified 2016-07-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000202796 SCV000614810 likely benign not specified 2017-06-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757695 SCV000886017 uncertain significance not provided 2017-10-03 criteria provided, single submitter clinical testing The PRX c.3496C>T; p.Pro1166Ser variant (rs147826200), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an non-Finnish European population frequency of 0.15% (identified on 194 out of 125,772 chromosomes) and is classified as likely benign/uncertain significance in ClinVar (ID:216835). The proline at position 1166 is moderately conserved, considering 11 species, and computational analyses of the effects of the p.Pro1166Ser variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Pro1166Ser variant cannot be determined with certainty.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.