ClinVar Miner

Submissions for variant NM_004563.4(PCK2):c.577C>T (p.Arg193Ter)

gnomAD frequency: 0.00005  dbSNP: rs753706965
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000732852 SCV000620559 uncertain significance not provided 2018-05-09 criteria provided, single submitter clinical testing The R193X variant in the PCK2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R193X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R193X as a variant of uncertain significance.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000625920 SCV000746506 pathogenic Phosphoenolpyruvate carboxykinase deficiency, mitochondrial 2017-12-03 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000732852 SCV000860847 uncertain significance not provided 2018-04-09 criteria provided, single submitter clinical testing
Invitae RCV000732852 SCV004425588 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 451808). This variant has not been reported in the literature in individuals affected with PCK2-related conditions. This variant is present in population databases (rs753706965, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg193*) in the PCK2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PCK2 cause disease.

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.