Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002232931 | SCV000831443 | uncertain significance | Ataxia-telangiectasia-like disorder | 2018-01-01 | criteria provided, single submitter | clinical testing | 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 tolerated, 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). This sequence change replaces glutamic acid with alanine at codon 423 of the MRE11 protein (p.Glu423Ala). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. |
| Ambry Genetics | RCV001010664 | SCV001170896 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-20 | criteria provided, single submitter | clinical testing | The p.E423A variant (also known as c.1268A>C), located in coding exon 11 of the MRE11A gene, results from an A to C substitution at nucleotide position 1268. The glutamic acid at codon 423 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is highly 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. |