Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575404 | SCV000673858 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-25 | criteria provided, single submitter | clinical testing | The p.F398L variant (also known as c.1194T>A), located in coding exon 10 of the MRE11A gene, results from a T to A substitution at nucleotide position 1194. The phenylalanine at codon 398 is replaced by leucine, 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 175000 alleles tested) in our clinical cohort. 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 | RCV002232659 | SCV002509428 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-07-11 | 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 398 of the MRE11 protein (p.Phe398Leu). 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. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 485816). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. This variant is not present in population databases (gnomAD no frequency). |