ClinVar Miner

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

dbSNP: rs886037952
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Total submissions: 23
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000257986 SCV000299373 pathogenic not provided 2021-10-05 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27264673, 27868344, 27338287, 28211982, 27681385, 28135719, 30368668, 31474318, 31370276, 32476286)
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
Eurofins NTD LLC (GA) 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 2021-08-28 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000490622 SCV001190249 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2019-05-04 criteria provided, single submitter clinical testing
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
CeGaT Center for Human Genetics Tuebingen RCV000257986 SCV001962241 pathogenic not provided 2021-08-01 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000490622 SCV001976798 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2021-10-05 criteria provided, single submitter clinical testing PM2, PP2, PP3, PP5
3billion RCV000490622 SCV002011951 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2021-10-02 criteria provided, single submitter clinical testing Same nucleotide change resulting in same amino acid change has been previously reported as de novoo and observed in at least four similarly affected unrelated individuals (PMID: 27264673, 28211982 and 27681385, PS2 and PS4). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000490622 SCV002557913 pathogenic Noonan syndrome-like disorder with loose anagen hair 2 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0101 - Gain of function is a known mechanism of disease in this gene and is associated with Noonan syndrome-like disorder with loose anagen hair 2 (MIM#617506) (PMID: 30348783). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a recurrent variant reported in multiple individuals with Noonan syndrome-like disorder with loose anagen hair 2 (MIM#617506) (ClinVar, Decipher, PMID: 33491856). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV002274002 SCV002559115 pathogenic Neurodevelopmental delay 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
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
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000257986 SCV001744847 pathogenic not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000257986 SCV001798142 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000257986 SCV001956324 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000257986 SCV001971001 pathogenic not provided no assertion criteria provided clinical testing

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