Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001236241 | SCV001408956 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-04-05 | 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 71 of the RAD51D protein (p.Leu71Phe). 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: 962391). 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 with a negative predictive value of 80%. 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 | RCV004944933 | SCV005485331 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-29 | criteria provided, single submitter | clinical testing | The p.L71F variant (also known as c.211C>T), located in coding exon 3 of the RAD51D gene, results from a C to T substitution at nucleotide position 211. The leucine at codon 71 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with breast and/or ovarian cancer (Golmard L et al. BMC Cancer, 2013 Oct;13:484). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |