Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001988226 | SCV002261581 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2021-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 469 of the RET protein (p.Asp469Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs772489699, ExAC 0.01%). This variant has been observed in individual(s) with clinical features of Hirschsprung disease (PMID: 10946353). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV002388977 | SCV002702468 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-25 | criteria provided, single submitter | clinical testing | The p.D469N variant (also known as c.1405G>A), located in coding exon 7 of the RET gene, results from a G to A substitution at nucleotide position 1405. The aspartic acid at codon 469 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is 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. |