Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000628768 | SCV000749674 | uncertain significance | Renal cell carcinoma | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 832 of the MET protein (p.Pro832Leu). This variant is present in population databases (rs781452657, gnomAD 0.003%). 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: 524888). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MET protein function with a positive predictive value of 80%. 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 | RCV001015703 | SCV001176566 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-01 | criteria provided, single submitter | clinical testing | The p.P832L variant (also known as c.2495C>T), located in coding exon 10 of the MET gene, results from a C to T substitution at nucleotide position 2495. The proline at codon 832 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Sema4, |
RCV001015703 | SCV002532127 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-24 | criteria provided, single submitter | curation | |
Gene |
RCV004767453 | SCV005376337 | uncertain significance | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |