Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220334 | SCV000273056 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-28 | criteria provided, single submitter | clinical testing | The p.F13L variant (also known as c.37T>C), located in coding exon 2 of the MRE11A gene, results from a T to C substitution at nucleotide position 37. The phenylalanine at codon 13 is replaced by leucine, an amino acid with highly similar properties. This alteration was reported in a study of 1297 cases of early-onset breast cancer and 1121 controls (Young EL et al. J. Med. Genet. 2016 06;53:366-76).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 | RCV000691356 | SCV000819132 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-06-19 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 13 of the MRE11 protein (p.Phe13Leu). This variant is present in population databases (rs149101834, gnomAD 0.03%). 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: 229733). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |