ClinVar Miner

Submissions for variant NM_001258392.3(CLPB):c.1592G>A (p.Arg531Gln)

dbSNP: rs1590753221
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000796680 SCV000936203 uncertain significance 3-methylglutaconic aciduria, type VIIB 2023-05-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 561 of the CLPB protein (p.Arg561Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant congenital neutropenia (PMID: 34115842). ClinVar contains an entry for this variant (Variation ID: 643064). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg561 amino acid residue in CLPB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32313153, 34140661; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
GeneDx RCV001766643 SCV001998797 pathogenic not provided 2022-07-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 34140661, 35499078, 34115842)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV002221585 SCV005328358 likely pathogenic Neutropenia, severe congenital, 9, autosomal dominant 2024-09-25 criteria provided, single submitter clinical testing
OMIM RCV002221585 SCV002499261 pathogenic Neutropenia, severe congenital, 9, autosomal dominant 2022-04-11 no assertion criteria provided literature only

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.