Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001050546 | SCV001214661 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with histidine at codon 375 of the MRE11 protein (p.Pro375His). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and histidine. 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. |
| Ambry Genetics | RCV002462288 | SCV002754685 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-01 | criteria provided, single submitter | clinical testing | The p.P375H variant (also known as c.1124C>A), located in coding exon 10 of the MRE11A gene, results from a C to A substitution at nucleotide position 1124. The proline at codon 375 is replaced by histidine, an amino acid with 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. |