Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217443 | SCV000274372 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-19 | criteria provided, single submitter | clinical testing | The p.D498N variant (also known as c.1492G>A), located in coding exon 12 of the MRE11A gene, results from a G to A substitution at nucleotide position 1492. The aspartic acid at codon 498 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Invitae | RCV002229550 | SCV002509595 | uncertain significance | Ataxia-telangiectasia-like disorder | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 498 of the MRE11 protein (p.Asp498Asn). This variant is present in population databases (rs564511708, gnomAD 0.007%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 37013556). ClinVar contains an entry for this variant (Variation ID: 230726). 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. 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. |