Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002042080 | SCV002110649 | uncertain significance | Renal cell carcinoma | 2023-07-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1350721). 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. This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1214 of the MET protein (p.Ala1214Thr). |
| Ambry Genetics | RCV002343889 | SCV002619337 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-14 | criteria provided, single submitter | clinical testing | The p.A1214T variant (also known as c.3640G>A), located in coding exon 17 of the MET gene, results from a G to A substitution at nucleotide position 3640. The alanine at codon 1214 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Baylor Genetics | RCV003475112 | SCV004192573 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-06-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004728855 | SCV005334699 | uncertain significance | not provided | 2024-01-24 | 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 |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004728855 | SCV005622924 | uncertain significance | not provided | 2024-07-12 | criteria provided, single submitter | clinical testing | The MET c.3640G>A (p.Ala1214Thr) variant has not been reported in individuals with MET-related conditions in the published literature. The frequency of this variant in the general population, 0.0000066 (1/152160 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |