Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022200 | SCV001183907 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-31 | criteria provided, single submitter | clinical testing | The p.I143V variant (also known as c.427A>G), located in coding exon 5 of the MRE11A gene, results from an A to G substitution at nucleotide position 427. The isoleucine at codon 143 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not 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. |
Invitae | RCV002236235 | SCV002509432 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 143 of the MRE11 protein (p.Ile143Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 824749). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. |