Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002235356 | SCV000957567 | uncertain significance | Renal cell carcinoma | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1159 of the MET protein (p.Ser1159Leu). This variant is present in population databases (rs375395179, gnomAD 0.002%). 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: 659937). 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. |
Ambry Genetics | RCV002336691 | SCV002618570 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-28 | criteria provided, single submitter | clinical testing | The p.S1159L variant (also known as c.3476C>T), located in coding exon 16 of the MET gene, results from a C to T substitution at nucleotide position 3476. The serine at codon 1159 is replaced by leucine, 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. |
Baylor Genetics | RCV004569726 | SCV005057866 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2024-02-15 | criteria provided, single submitter | clinical testing |