Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002239666 | SCV002509550 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with glutamine at codon 245 of the MRE11 protein (p.His245Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV003164334 | SCV003879798 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-05 | criteria provided, single submitter | clinical testing | The p.H245Q variant (also known as c.735T>G), located in coding exon 7 of the MRE11A gene, results from a T to G substitution at nucleotide position 735. The histidine at codon 245 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |