Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001326762 | SCV001517810 | uncertain significance | Ataxia-telangiectasia-like disorder | 2020-01-14 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MRE11-related conditions. This variant is present in population databases (rs764734589, ExAC 0.001%). This sequence change replaces valine with isoleucine at codon 458 of the MRE11 protein (p.Val458Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. |
Ambry Genetics | RCV002462936 | SCV002756146 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-08 | criteria provided, single submitter | clinical testing | The p.V458I variant (also known as c.1372G>A), located in coding exon 12 of the MRE11A gene, results from a G to A substitution at nucleotide position 1372. The valine at codon 458 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |