Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218270 | SCV000275013 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-01 | criteria provided, single submitter | clinical testing | The p.D113N variant (also known as c.337G>A), located in coding exon 4 of the MRE11A gene, results from a G to A substitution at nucleotide position 337. The aspartic acid at codon 113 is replaced by asparagine, an amino acid with highly similar properties. A similar variant that affects the same amino acid residue, p.D113G (c.338A>G), was reported in an individual who was compound heterozygous for another MRE11A variant, and had a Nijmegen breakage syndrome (NBS)-like phenotype with severe microcephaly (Matsumoto Y et al. DNA Repair (Amst.) 2011 Mar;10(3):314-21). This amino acid position is highly 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 p.D113N remains unclear. |
Invitae | RCV002228957 | SCV000820107 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 113 of the MRE11 protein (p.Asp113Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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. ClinVar contains an entry for this variant (Variation ID: 231234). 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"). 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. |