Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024543 | SCV001186575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | The p.F193L variant (also known as c.579T>G), located in coding exon 6 of the MRE11A gene, results from a T to G substitution at nucleotide position 579. The phenylalanine at codon 193 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001304017 | SCV001493284 | uncertain significance | Ataxia-telangiectasia-like disorder | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 193 of the MRE11 protein (p.Phe193Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. 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: 825978). 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. |