Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001802751 | SCV002049902 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2021-02-15 | criteria provided, single submitter | clinical testing | The RAD51D c.224T>C; p.Leu75Pro variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 75 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.332). Due to limited information, the clinical significance of the p.Leu75Pro variant is uncertain at this time. |
| Labcorp Genetics |
RCV001802751 | SCV002294510 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 75 of the RAD51D protein (p.Leu75Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 1331092). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51D protein function. 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. |
| Ambry Genetics | RCV002425078 | SCV002728833 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-27 | criteria provided, single submitter | clinical testing | The p.L75P variant (also known as c.224T>C), located in coding exon 3 of the RAD51D gene, results from a T to C substitution at nucleotide position 224. The leucine at codon 75 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |