Submissions for variant NM_005188.4(CBL):c.2484G>A (p.Pro828=)

gnomAD frequency: 0.00166  dbSNP: rs149533467

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000154693	SCV000167557	benign	not specified	2013-01-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154693	SCV000204371	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Pro828Pro in Exon 16 of CBL: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.5% (20/3738) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs149533467).
Invitae	RCV000460543	SCV000555928	benign	RASopathy	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001103081	SCV001259799	benign	CBL-related disorder	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154693	SCV001362204	benign	not specified	2019-09-24	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813232	SCV002060759	uncertain significance	Noonan syndrome and Noonan-related syndrome	2016-12-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000154693	SCV002071659	benign	not specified	2019-12-26	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV002227048	SCV002506125	benign	not provided	2022-01-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426536	SCV002740439	benign	Cardiovascular phenotype	2020-01-06	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315532	SCV004016979	benign	Juvenile myelomonocytic leukemia	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002227048	SCV004701266	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CBL: BP4, BP7, BS1