Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000458477 | SCV000553305 | uncertain significance | Renal cell carcinoma | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 267 of the MET protein (p.Glu267Lys). This variant is present in population databases (rs755954919, gnomAD 0.0009%). 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: 411894). 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. |
Fulgent Genetics, |
RCV000765916 | SCV000897336 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001821293 | SCV002071909 | uncertain significance | not specified | 2021-10-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002418422 | SCV002678099 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-05 | criteria provided, single submitter | clinical testing | The p.E267K variant (also known as c.799G>A), located in coding exon 1 of the MET gene, results from a G to A substitution at nucleotide position 799. The glutamic acid at codon 267 is replaced by lysine, an amino acid with 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. |
Baylor Genetics | RCV003470495 | SCV004192529 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-08-28 | criteria provided, single submitter | clinical testing |