Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002443568 | SCV002736483 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-01 | criteria provided, single submitter | clinical testing | The p.G751E variant (also known as c.2252G>A), located in coding exon 12 of the RET gene, results from a G to A substitution at nucleotide position 2252. The glycine at codon 751 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003098749 | SCV003450863 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-10-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 751 of the RET protein (p.Gly751Glu). This variant is present in population databases (rs778292678, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 1788459). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |