Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000123298 | SCV000166605 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-07-11 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 489 of the RET protein (p.Asp489Glu). 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 136101). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is present in population databases (rs372648203, gnomAD 0.0009%). |
| Mendelics | RCV000709113 | SCV000838383 | uncertain significance | Multiple endocrine neoplasia type 2A | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001011534 | SCV001171867 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-21 | criteria provided, single submitter | clinical testing | The p.D489E variant (also known as c.1467C>A), located in coding exon 7 of the RET gene, results from a C to A substitution at nucleotide position 1467. The aspartic acid at codon 489 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |