Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001229704 | SCV001402158 | uncertain significance | Renal cell carcinoma | 2020-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with phenylalanine at codon 624 of the MET protein (p.Cys624Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MET-related conditions. This variant is not present in population databases (ExAC no frequency). |
Ambry Genetics | RCV002411843 | SCV002721077 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-05 | criteria provided, single submitter | clinical testing | The p.C624F variant (also known as c.1871G>T), located in coding exon 6 of the MET gene, results from a G to T substitution at nucleotide position 1871. The cysteine at codon 624 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |