Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040261 | SCV001203823 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2019-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 702 of the RET protein (p.Asn702Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. 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 tolerated, 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 variant has not been reported in the literature in individuals with RET-related conditions. |
| Ambry Genetics | RCV002416344 | SCV002724582 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-18 | criteria provided, single submitter | clinical testing | The p.N702S variant (also known as c.2105A>G), located in coding exon 11 of the RET gene, results from an A to G substitution at nucleotide position 2105. The asparagine at codon 702 is replaced by serine, an amino acid with highly 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. |