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: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195707 SCV000255227 likely benign Charcot-Marie-Tooth disease type 4 2020-11-12 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001094576 SCV000413245 uncertain significance Charcot-Marie-Tooth disease, demyelinating, type 4F 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415792 SCV000493487 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000415792 SCV000583132 likely benign not provided 2020-09-22 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25025039, 26257172, 26392352, 32376792)
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282155 SCV000604941 uncertain significance none provided 2019-09-13 criteria provided, single submitter clinical testing The PRX c.823C>A; p.Leu275Ile variant (rs200033507), is reported in the literature in individuals affected with Charcot-Marie-Tooth (CMT) disease or hereditary motor neuropathy, but did not segregate with disease in at least two families, suggesting the variant is not causative for disease (Antoniadi 2015, Hoyer 2014). This variant is reported as uncertain significance by multiple laboratories in ClinVar (Variation ID: 216836), and is found in the non-Finnish European population with an allele frequency of 0.22% (153/69,546 alleles) in the Genome Aggregation Database. The leucine at codon 275 is moderately conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: probably damaging) predict conflicting effects of this variant on protein structure/function. Thus, based on available information, the clinical significance of the p.Leu275Ile variant cannot be determined with certainty. References: Antoniadi T et al. Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability. BMC Med Genet. 2015 Sep 21;16:84. Hoyer et al. Genetic diagnosis of Charcot-Marie-Tooth disease in a population by next-generation sequencing. Biomed Res Int. 2014 2014: 210401.
Athena Diagnostics Inc RCV000493878 SCV000614816 likely benign not specified 2016-09-14 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
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173081 SCV001336157 likely benign Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Practice for Gait Abnormalities, David Pomarino,Competency Network Toe Walking c/o Practice Pomarino RCV001449601 SCV001652703 uncertain significance Toe walking 2021-04-27 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000415792 SCV001713815 uncertain significance not provided 2020-07-24 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000415792 SCV001809704 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000415792 SCV001924551 uncertain significance not provided no assertion criteria provided clinical testing

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.