Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222276 | SCV000276036 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-23 | criteria provided, single submitter | clinical testing | The p.F248L variant (also known as c.742T>C), located in coding exon 5 of the RAD51C gene, results from a T to C substitution at nucleotide position 742. The phenylalanine at codon 248 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 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 p.F248L remains unclear. |
| Labcorp Genetics |
RCV001853572 | SCV002115000 | uncertain significance | Fanconi anemia complementation group O | 2020-12-01 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 232017). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 248 of the RAD51C protein (p.Phe248Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. |
| Baylor Genetics | RCV003469048 | SCV004207926 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-10-01 | criteria provided, single submitter | clinical testing |