Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021593 | SCV001183229 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-13 | criteria provided, single submitter | clinical testing | The p.R133P variant (also known as c.398G>C), located in coding exon 3 of the RET gene, results from a G to C substitution at nucleotide position 398. The arginine at codon 133 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is well 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 |
RCV001340144 | SCV001533943 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2020-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with proline at codon 133 of the RET protein (p.Arg133Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RET-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |