ClinVar Miner

Submissions for variant NM_000245.4(MET):c.2684C>T (p.Thr895Met)

gnomAD frequency: 0.00011  dbSNP: rs199502137
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000541456 SCV000623412 likely benign Renal cell carcinoma 2024-01-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV001016448 SCV001177406 likely benign Hereditary cancer-predisposing syndrome 2022-01-25 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 RCV001591188 SCV001822406 uncertain significance not provided 2024-02-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002476079 SCV002793653 uncertain significance Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 2021-12-08 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003444568 SCV004171467 uncertain significance Papillary renal cell carcinoma type 1 2023-10-16 criteria provided, single submitter clinical testing The MET c.2738C>T (p.Thr913Met) missense change has a maximum subpopulation frequency of 0.041% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with hereditary papillary renal cell carcinoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001591188 SCV005622913 uncertain significance not provided 2024-10-11 criteria provided, single submitter clinical testing The MET c.2738C>T (p.Thr913Met) variant has not been reported in individuals with MET-related conditions in the published literature. The frequency of this variant in the general population, 0.00041 (10/24178 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences RCV003392361 SCV004119074 uncertain significance MET-related disorder 2024-08-14 no assertion criteria provided clinical testing The MET c.2738C>T variant is predicted to result in the amino acid substitution p.Thr913Met. This variant is reported as c.2684C>T (p.Thr895Met) on an alternate transcript (NM_000245). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.041% of alleles in individuals of African descent in gnomAD and has been interpreted as uncertain and likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/454219). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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