Submissions for variant NM_005188.4(CBL):c.2216C>T (p.Ser739Phe)

gnomAD frequency: 0.00006  dbSNP: rs2227986

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000680285	SCV000057271	likely benign	not provided	2016-06-08	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	RCV000038355	SCV000062027	likely benign	not specified	2017-04-10	criteria provided, single submitter	clinical testing	p.Ser739Phe in exon 14 of CBL: This variant is not expected to have clinical sig nificance because it has been identified in 0.2% (38/16502) of South Asian chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs2227986).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089042	SCV000254838	likely benign	RASopathy	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000296277	SCV000367777	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813228	SCV002060496	likely benign	Noonan syndrome and Noonan-related syndrome	2020-08-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000038355	SCV003933799	likely benign	not specified	2023-05-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000680285	SCV004129485	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	CBL: BS1
PreventionGenetics, part of Exact Sciences	RCV000296277	SCV004770279	likely benign	CBL-related disorder	2020-04-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).