Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002231672 | SCV000623445 | uncertain significance | Renal cell carcinoma | 2017-02-02 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MET-related disease. This sequence change replaces leucine with glutamine at codon 1335 of the MET protein (p.Leu1335Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. |
Ambry Genetics | RCV001021644 | SCV001183286 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-03 | criteria provided, single submitter | clinical testing | The p.L1335Q variant (also known as c.4004T>A), located in coding exon 20 of the MET gene, results from a T to A substitution at nucleotide position 4004. The leucine at codon 1335 is replaced by glutamine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Gene |
RCV001775840 | SCV002013827 | uncertain significance | not provided | 2024-02-20 | criteria provided, single submitter | clinical testing | Not observed at a 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 |