Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012092 | SCV001172504 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-29 | criteria provided, single submitter | clinical testing | The p.I513T variant (also known as c.1538T>C), located in coding exon 4 of the MET gene, results from a T to C substitution at nucleotide position 1538. The isoleucine at codon 513 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001323863 | SCV001514798 | uncertain significance | Renal cell carcinoma | 2020-01-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with MET-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 513 of the MET protein (p.Ile513Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. |