Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000628760 | SCV000749666 | 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 arginine, which is basic and polar, at codon 386 of the MET protein (p.Leu386Arg). 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: 524881). 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. |
Fulgent Genetics, |
RCV000765917 | SCV000897337 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003302970 | SCV003996611 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | The p.L386R variant (also known as c.1157T>G), located in coding exon 1 of the MET gene, results from a T to G substitution at nucleotide position 1157. The leucine at codon 386 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV005000398 | SCV005622878 | uncertain significance | not provided | 2024-04-28 | criteria provided, single submitter | clinical testing | The MET c.1157T>G (p.Leu386Arg) variant has not been reported in individuals with MET-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). 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. |