Submissions for variant NM_005188.4(CBL):c.1641T>C (p.Pro547=)

gnomAD frequency: 0.00074  dbSNP: rs61755280

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038353	SCV000062025	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Pro547Pro in Exon 11 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. It has been identified in 0.2% (12/7020) of Euro pean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs61755280).
GeneDx	RCV000038353	SCV000167554	benign	not specified	2012-01-17	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000124140	SCV000259371	benign	RASopathy	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000038353	SCV000310870	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000354617	SCV000367767	benign	CBL-related disorder	2018-01-13	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	RCV000038353	SCV001437406	likely benign	not specified	2020-09-06	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813346	SCV002060490	benign	Noonan syndrome and Noonan-related syndrome	2021-04-10	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000038353	SCV002064851	benign	not specified	2020-04-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399378	SCV002709367	likely benign	Cardiovascular phenotype	2022-03-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	RCV003315561	SCV004016970	benign	Juvenile myelomonocytic leukemia	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001727536	SCV004129482	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	CBL: BP4, BP7
Breakthrough Genomics, Breakthrough Genomics	RCV001727536	SCV005211137	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000038353	SCV001926698	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727536	SCV001976314	likely benign	not provided		no assertion criteria provided	clinical testing