ClinVar Miner

Submissions for variant NM_181882.3(PRX):c.3673G>A (p.Val1225Met)

gnomAD frequency: 0.00009  dbSNP: rs140880177
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001039383 SCV001202913 uncertain significance Charcot-Marie-Tooth disease type 4 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1225 of the PRX protein (p.Val1225Met). This variant is present in population databases (rs140880177, gnomAD 0.1%). This missense change has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 31372974). ClinVar contains an entry for this variant (Variation ID: 837941). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Illumina Laboratory Services, Illumina RCV001135980 SCV001295792 benign Charcot-Marie-Tooth disease type 4F 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx RCV005255641 SCV005908449 uncertain significance not provided 2024-10-10 criteria provided, single submitter clinical testing Reported in patients with chemotherapy-induced peripheral neuropathy or Charcot-Marie-Tooth in the published literature; however, zygosity or whether a second variant in the PRX gene was identified was not reported (PMID: 25164601, 25614874, 31372974); Reported as a heterozygous variant in a family with congenital cataract in the published literature; however, a second variant in the PRX gene was not reported (PMID: 27081207); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25164601, 25614874, 31372974, 27081207)

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.