Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000680286 | SCV000057274 | benign | not provided | 2021-03-05 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 27244893, 24896146, 31057598, 32604168) |
Laboratory for Molecular Medicine, |
RCV000038358 | SCV000062030 | uncertain significance | not specified | 2013-06-21 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Pro782Leu varia nt in CBL has been identified by our laboratory in this patient's son, however i t has not been seen in the literature. This variant has been identified in 0.7% (30/4398) of African American chromosomes from a large population study by the N HLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs222907 3). Computational analyses (biochemical amino acid properties, conservation, Ali gnGVGD, PolyPhen2, and SIFT) suggest that the Pro782Leu variant may impact the p rotein, though this information is not predictive enough to determine pathogenic ity. In summary, additional information is needed to fully assess the clinical s ignificance of the Pro782Leu variant. |
Invitae | RCV001088335 | SCV000260563 | benign | RASopathy | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000106328 | SCV000367779 | 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, |
RCV000038358 | SCV001426998 | benign | not specified | 2020-07-27 | criteria provided, single submitter | clinical testing | Variant summary: CBL c.2345C>T (p.Pro782Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00078 in 251460 control chromosomes, predominantly at a frequency of 0.0082 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3280 fold of the estimated maximal expected allele frequency for a pathogenic variant in CBL causing Noonan Syndrome And Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.2345C>T has been reported in the literature in at least one individual affected with Noonan Syndrome (Justino_2015). This report does not provide unequivocal conclusions about association of the variant with Noonan Syndrome And Related Conditions. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
ARUP Laboratories, |
RCV000680286 | SCV001471960 | benign | not provided | 2020-05-22 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001813231 | SCV002060498 | benign | Noonan syndrome and Noonan-related syndrome | 2020-05-01 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000038358 | SCV002064862 | benign | not specified | 2021-03-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002426535 | SCV002731881 | likely benign | Cardiovascular phenotype | 2019-11-20 | 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. |
Ce |
RCV000680286 | SCV004129487 | benign | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | CBL: BS1, BS2 |
Institute of Molecular Pathology and Immunology of the University of Porto |
RCV000106328 | SCV000143826 | not provided | CBL-related disorder | no assertion provided | not provided | ||
Clinical Genetics, |
RCV000038358 | SCV001925329 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000038358 | SCV001958387 | benign | not specified | no assertion criteria provided | clinical testing |