Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021471 | SCV001183091 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-13 | criteria provided, single submitter | clinical testing | The p.V1312I variant (also known as c.3934G>A), located in coding exon 19 of the MET gene, results from a G to A substitution at nucleotide position 3934. The valine at codon 1312 is replaced by isoleucine, an amino acid with highly 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 |
RCV001226697 | SCV001399018 | uncertain significance | Renal cell carcinoma | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1312 of the MET protein (p.Val1312Ile). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 824400). 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 with a negative 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 |
RCV001551296 | SCV001771773 | uncertain significance | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); 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; This variant is associated with the following publications: (PMID: 27535533, 20949619) |
| Baylor Genetics | RCV003461389 | SCV004192499 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-09-25 | criteria provided, single submitter | clinical testing |