Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002441757 | SCV002747654 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-06 | criteria provided, single submitter | clinical testing | The p.G939V variant (also known as c.2816G>T), located in coding exon 12 of the MET gene, results from a G to T substitution at nucleotide position 2816. The glycine at codon 939 is replaced by valine, an amino acid with dissimilar 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. |
Labcorp Genetics |
RCV003594299 | SCV004254018 | uncertain significance | Renal cell carcinoma | 2023-06-09 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1796383). This variant has not been reported in the literature in individuals affected with MET-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 939 of the MET protein (p.Gly939Val). |