Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001034644 | SCV000547397 | uncertain significance | Ataxia-telangiectasia-like disorder | 2019-04-09 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MRE11A-related disease. This sequence change replaces aspartic acid with alanine at codon 163 of the MRE11A protein (p.Asp163Ala). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and alanine. |
| Ambry Genetics | RCV000475404 | SCV000662148 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-15 | criteria provided, single submitter | clinical testing | The p.D163A variant (also known as c.488A>C), located in coding exon 5 of the MRE11A gene, results from an A to C substitution at nucleotide position 488. The aspartic acid at codon 163 is replaced by alanine, an amino acid with dissimilar 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. |