Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000798718 | SCV000938347 | uncertain significance | Fanconi anemia complementation group O | 2022-03-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 111 of the RAD51C protein (p.Leu111Phe). 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"). ClinVar contains an entry for this variant (Variation ID: 644736). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). |
Ambry Genetics | RCV002458445 | SCV002611629 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-11-27 | criteria provided, single submitter | clinical testing | The p.L111F variant (also known as c.331C>T), located in coding exon 2 of the RAD51C gene, results from a C to T substitution at nucleotide position 331. The leucine at codon 111 is replaced by phenylalanine, 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 0.001% (greater than 120000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.L111F remains unclear. |