Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000235726 | SCV000294274 | uncertain significance | Renal cell carcinoma | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1058 of the MET protein (p.Ser1058Pro). This variant is present in population databases (rs771328219, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 246636). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000567924 | SCV000673722 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-02 | 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 |
RCV001764221 | SCV002009028 | uncertain significance | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in tumor and adjacent normal tissue from a patient with non-small cell lung cancer (PMID: 15735036); This variant is associated with the following publications: (PMID: 19037978, 19333071, 18340114, 23275061, 20139696, 31226345, 32964978, 15735036) |
| Baylor Genetics | RCV003475844 | SCV004192577 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2024-02-27 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001764221 | SCV005622916 | uncertain significance | not provided | 2024-11-16 | criteria provided, single submitter | clinical testing | The MET c.3172T>C (p.Ser1058Pro) variant has been reported in the published literature in an individual with breast and/or ovarian cancer (PMID: 27153395 (2016)). The frequency of this variant in the general population, 0.000064 (2/31410 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 predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |