Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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. |
Gene |
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, |
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. |
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. |
Prevention |
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. |