Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001026385 | SCV001188755 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-01 | criteria provided, single submitter | clinical testing | The p.I25L variant (also known as c.73A>C), located in coding exon 1 of the RAD51D gene, results from an A to C substitution at nucleotide position 73. The isoleucine at codon 25 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV001862366 | SCV002263828 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2020-12-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 827019). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This sequence change replaces isoleucine with leucine at codon 25 of the RAD51D protein (p.Ile25Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is not present in population databases (ExAC no frequency). |