Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001016678 | SCV001177659 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-03 | criteria provided, single submitter | clinical testing | The p.D94G variant (also known as c.281A>G), located in coding exon 1 of the MET gene, results from an A to G substitution at nucleotide position 281. The aspartic acid at codon 94 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
Labcorp Genetics |
RCV001297354 | SCV001486366 | uncertain significance | Renal cell carcinoma | 2023-08-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs368328347, gnomAD 0.007%). 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 not expected to disrupt MET protein function. ClinVar contains an entry for this variant (Variation ID: 821849). This variant has not been reported in the literature in individuals affected with MET-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 94 of the MET protein (p.Asp94Gly). |
Gene |
RCV003223686 | SCV003919486 | uncertain significance | not provided | 2022-10-20 | 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 |