Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000476289 | SCV001189238 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-03 | criteria provided, single submitter | clinical testing | The p.Q259E variant (also known as c.775C>G), located in coding exon 7 of the MRE11A gene, results from a C to G substitution at nucleotide position 775. The glutamine at codon 259 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001351570 | SCV001546058 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 259 of the MRE11 protein (p.Gln259Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. 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. 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. |