Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001312213 | SCV000553301 | uncertain significance | Renal cell carcinoma | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 645 of the MET protein (p.Gly645Arg). This variant is present in population databases (rs763849125, gnomAD 0.006%). 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: 411891). 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. |
Mendelics | RCV000472256 | SCV000838257 | uncertain significance | Papillary renal cell carcinoma type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001013640 | SCV001174253 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-21 | criteria provided, single submitter | clinical testing | The p.G645R variant (also known as c.1933G>A), located in coding exon 6 of the MET gene, results from a G to A substitution at nucleotide position 1933. The glycine at codon 645 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not 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. |
Fulgent Genetics, |
RCV002481472 | SCV002792645 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 | 2021-10-11 | criteria provided, single submitter | clinical testing | |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV003225728 | SCV003806797 | uncertain significance | Arthrogryposis, distal, IIa 11 | 2022-09-28 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderated, BP4 supporting |