Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000571233 | SCV000666413 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-24 | criteria provided, single submitter | clinical testing | The p.I470V variant (also known as c.1408A>G), located in coding exon 12 of the MRE11A gene, results from an A to G substitution at nucleotide position 1408. The isoleucine at codon 470 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 120000 alleles tested) in our clinical cohort. 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 this alteration remains unclear. |
Invitae | RCV001349029 | SCV001543356 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 470 of the MRE11 protein (p.Ile470Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. 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: "Possibly 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. |