Submissions for variant NM_005188.4(CBL):c.2360G>A (p.Arg787His)

gnomAD frequency: 0.00011  dbSNP: rs200220863

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000033371	SCV000057276	likely benign	not provided	2016-09-30	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	RCV000473552	SCV000543495	likely benign	RASopathy	2023-12-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001582505	SCV001821407	uncertain significance	not specified	2022-11-28	criteria provided, single submitter	clinical testing	Variant summary: CBL c.2360G>A (p.Arg787His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251462 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2360G>A in individuals affected with Noonan Syndrome-Like Disorder and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite this variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000033371	SCV001798114	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001582505	SCV001919619	benign	not specified		no assertion criteria provided	clinical testing