ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*1028C>A (rs200033507)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000493878 SCV000604941 uncertain significance not specified 2016-06-30 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000493878 SCV000614816 likely benign not specified 2016-09-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415792 SCV000493487 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000415792 SCV000856117 uncertain significance not provided 2017-08-24 criteria provided, single submitter clinical testing
GeneDx RCV000493878 SCV000583132 uncertain significance not specified 2017-05-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PRX gene. The L275I variant has been previously reported in two families with CMT who also had another variant on the opposite allele; however, the L275I variant did not segregate with disease in either family, leading the authors to conclude that it is not pathogenic (Hoyer et al., 2014). The L275I variant is observed in 7/4404 (0.2%) alleles from individuals of non-Finnish European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L275I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000195707 SCV000413245 uncertain significance Charcot-Marie-Tooth disease type 4 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000195707 SCV000255227 uncertain significance Charcot-Marie-Tooth disease type 4 2018-06-25 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 275 of the PRX protein (p.Leu275Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs200033507, ExAC 0.2%). This variant has been reported in families and individuals affected with Charcot-Marie-Tooth disease and hereditary motor neuropathy (PMID: 25025039, 26257172, 26392352). However, in one family this variant was not present in all affected individuals (PMID: 25025039) and in an unrelated individual a second PRX variant was not identified (PMID: 26392352). ClinVar contains an entry for this variant (Variation ID: 216836). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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.