Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220333 | SCV000276820 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-03 | criteria provided, single submitter | clinical testing | The p.R502H variant (also known as c.1505G>A), located in coding exon 13 of the MRE11A gene, results from a G to A substitution at nucleotide position 1505. The arginine at codon 502 is replaced by histidine, 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. |
Gene |
RCV001753673 | SCV001986897 | uncertain significance | not provided | 2019-04-03 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV002229285 | SCV002509547 | uncertain significance | Ataxia-telangiectasia-like disorder | 2023-04-07 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 232638). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. This variant is present in population databases (rs767097795, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 502 of the MRE11 protein (p.Arg502His). |