Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561701 | SCV000662150 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-28 | criteria provided, single submitter | clinical testing | The p.N227K variant (also known as c.681C>G), located in coding exon 7 of the MRE11A gene, results from a C to G substitution at nucleotide position 681. The asparagine at codon 227 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001068353 | SCV001233460 | uncertain significance | Ataxia-telangiectasia-like disorder | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 227 of the MRE11 protein (p.Asn227Lys). This variant is present in population databases (no rsID available, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 479733). 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. |