ClinVar Miner

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

gnomAD frequency: 0.00153  dbSNP: rs35284565
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Total submissions: 6
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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
Invitae RCV000199168 SCV000252747 benign Renal cell carcinoma 2021-12-12 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: 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

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