ClinVar Miner

Submissions for variant NM_002709.3(PPP1CB):c.146C>G (p.Pro49Arg) (rs886037952)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000257986 SCV000299373 pathogenic not provided 2016-09-08 criteria provided, single submitter clinical testing The P49R variant in the PPP1CB gene has been reported previously as a de novo variant in three unrelated individuals with macrocephaly, developmental delay, and dysmorphic features as well as variable additional features including short stature and congenital heart defects (Gripp et al., 2016). The P49R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P49R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P49R as a pathogenic variant.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000257986 SCV000609586 pathogenic not provided 2017-08-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000257986 SCV000861880 pathogenic not provided 2018-06-15 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000257986 SCV000928041 pathogenic not provided 2018-11-07 criteria provided, single submitter clinical testing
Invitae RCV000257986 SCV000933113 pathogenic not provided 2019-05-21 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 49 of the PPP1CB protein (p.Pro49Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in the literature in individuals affected with Noonan syndrome-like disorder with loose anagen hair (NSLDH) (PMID: 27681385, 28211982) and also been observed to be de novo in individuals affected with NSLDH (PMID: 27264673, 27681385, 27868344). ClinVar contains an entry for this variant (Variation ID: 254648). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001265940 SCV001444112 pathogenic Inborn genetic diseases 2016-07-06 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000257986 SCV001447547 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
OMIM RCV000490622 SCV000579309 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2017-05-31 no assertion criteria provided literature only
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000490622 SCV001190249 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2019-05-04 no assertion criteria provided clinical testing
Service de Génétique Moléculaire,Hôpital Robert Debré RCV001251211 SCV001426696 pathogenic Noonan syndrome no assertion criteria provided clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV000490622 SCV001428110 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2019-01-01 no assertion criteria provided clinical testing
University of Washington Center for Mendelian Genomics, University of Washington RCV001257999 SCV001434812 likely pathogenic Dandy-Walker syndrome no assertion criteria provided research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000490622 SCV001438015 likely pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2018-06-29 no assertion criteria provided research
Coyote Medical Laboratory (Beijing),Coyote RCV000490622 SCV001441279 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2018-05-28 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.