Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002233243 | SCV000820332 | uncertain significance | Ataxia-telangiectasia-like disorder | 2018-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with proline at codon 601 of the MRE11 protein (p.Thr601Pro). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MRE11-related disease. 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 and their clinical significance is uncertain. 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 | RCV001013229 | SCV001173786 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-01 | criteria provided, single submitter | clinical testing | The p.T601P variant (also known as c.1801A>C), located in coding exon 15 of the MRE11A gene, results from an A to C substitution at nucleotide position 1801. The threonine at codon 601 is replaced by proline, an amino acid with highly 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. |