Submissions for variant NM_005188.4(CBL):c.1365TGA[7] (p.Asp460dup)

dbSNP: rs397507494

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001703887	SCV000057262	benign	not provided	2020-06-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32041989)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038351	SCV000062023	likely benign	not specified	2017-04-10	criteria provided, single submitter	clinical testing	p.Asp460dup in exon 9 of CBL: This variant is not expected to have clinical sign ificance because it has been identified in 0.5% (126/25640) Finnish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; db SNP rs777654641).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000033357	SCV000555929	likely benign	RASopathy	2024-01-29	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001703887	SCV002050149	likely benign	not provided	2021-07-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000038351	SCV002071112	likely benign	not specified	2021-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000038351	SCV002511710	benign	not specified	2023-05-15	criteria provided, single submitter	clinical testing	Variant summary: CBL c.1380_1382dupTGA (p.Asp460dup) results in an in-frame duplication that is predicted to duplicate one amino acid into the encoded protein. The variant allele was found at a frequency of 0.00078 in 250258 control chromosomes (gnomAD). The observed variant frequency is approximately 312 fold of the estimated maximal expected allele frequency for a pathogenic variant in CBL causing Noonan Syndrome And Related Conditions (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1380_1382dupTGA in individuals affected with Noonan Syndrome And Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters have assessed the variant since 2014: four classified the variant as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001703887	SCV004811046	benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	CBL: BS1, BS2