Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002233509 | SCV000764124 | uncertain significance | Ataxia-telangiectasia-like disorder | 2017-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with tyrosine at codon 131 of the MRE11 protein (p.Asp131Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MRE11-related disease. This variant is not present in population databases (ExAC no frequency). |
Athena Diagnostics Inc | RCV000992328 | SCV001144544 | uncertain significance | not provided | 2019-03-21 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002461947 | SCV002756118 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-26 | criteria provided, single submitter | clinical testing | The p.D131Y variant (also known as c.391G>T), located in coding exon 4 of the MRE11A gene, results from a G to T substitution at nucleotide position 391. The aspartic acid at codon 131 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |