Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000813026 | SCV000953359 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with histidine at codon 239 of the MRE11 protein (p.Asp239His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV002462178 | SCV002755561 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-11 | criteria provided, single submitter | clinical testing | The p.D239H variant (also known as c.715G>C), located in coding exon 7 of the MRE11A gene, results from a G to C substitution at nucleotide position 715. The aspartic acid at codon 239 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |