Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001304000 | SCV001493267 | uncertain significance | Renal cell carcinoma | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 107 of the MET protein (p.Leu107Val). This variant is not present in population databases (gnomAD no frequency). 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: 1006887). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Gene |
RCV003318679 | SCV004022971 | uncertain significance | not provided | 2023-07-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV004036298 | SCV005038266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-19 | criteria provided, single submitter | clinical testing | The p.L107V variant (also known as c.319T>G), located in coding exon 1 of the MET gene, results from a T to G substitution at nucleotide position 319. The leucine at codon 107 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Clinical Genomics Laboratory, |
RCV003318679 | SCV005047125 | uncertain significance | not provided | 2024-03-13 | criteria provided, single submitter | clinical testing | A MET c.319T>G (p.Leu107Val) variant was identified at a near heterozygous allelic fraction of 48.7%, a frequency which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature and is only observed on 1/152,132 alleles in the general population (gnomAD v.4.0.0), indicating it is not a common variant. It has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters (ClinVar ID: 1006887). Computational predictors suggest that the variant does not impact MET function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the MET c.319T>G (p.Leu107Val) variant is uncertain at this time. |