Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001361533 | SCV001557509 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2020-07-15 | criteria provided, single submitter | clinical testing | 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with RET-related conditions. This sequence change replaces serine with threonine at codon 159 of the RET protein (p.Ser159Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002341761 | SCV002640375 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-16 | criteria provided, single submitter | clinical testing | The p.S159T variant (also known as c.475T>A), located in coding exon 3 of the RET gene, results from a T to A substitution at nucleotide position 475. The serine at codon 159 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |