Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000817508 | SCV000958072 | uncertain significance | Renal cell carcinoma | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 477 of the MET protein (p.Val477Glu). This variant is present in population databases (no rsID available, 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: 660337). 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. |
| Gene |
RCV003153861 | SCV003842339 | uncertain significance | not provided | 2022-09-15 | 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 |
| Baylor Genetics | RCV003467481 | SCV004192587 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-05-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004028916 | SCV005037824 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-07 | criteria provided, single submitter | clinical testing | The p.V477E variant (also known as c.1430T>A), located in coding exon 3 of the MET gene, results from a T to A substitution at nucleotide position 1430. The valine at codon 477 is replaced by glutamic acid, 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. |