ClinVar Miner

Submissions for variant NM_000245.4(MET):c.654G>A (p.Arg218=)

gnomAD frequency: 0.00153  dbSNP: rs35284565
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000079498 SCV000111380 benign not specified 2012-09-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000199168 SCV000252747 benign Renal cell carcinoma 2024-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000572842 SCV000664673 likely benign Hereditary cancer-predisposing syndrome 2015-03-23 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.
GeneDx RCV000079498 SCV000724899 likely benign not specified 2018-02-27 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000079498 SCV000917633 benign not specified 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The MET c.654G>A (p.Arg218Arg) variant involves the alteration of a non-conserved nucleotide located in the Sema domain (IPR001627) (InterPro), resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 125/276368 control chromosomes (1 homozygote; gnomAD) at a frequency of 0.0004523, which is approximately 302 times the estimated maximal expected allele frequency of a pathogenic MET variant (0.0000015), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Sema4, Sema4 RCV000572842 SCV002532176 benign Hereditary cancer-predisposing syndrome 2020-12-01 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000079498 SCV005090765 likely benign not specified 2024-07-31 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV004704840 SCV005221491 likely benign not provided criteria provided, single submitter not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.