Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002434946 | SCV002745073 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-31 | criteria provided, single submitter | clinical testing | The p.D850V variant (also known as c.2549A>T), located in coding exon 14 of the RET gene, results from an A to T substitution at nucleotide position 2549. The aspartic acid at codon 850 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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 |
RCV003101955 | SCV003269766 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-05-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 850 of the RET protein (p.Asp850Val). 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: "Deleterious"; PolyPhen-2: "Probably 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. |