Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000813891 | SCV000954273 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 135 of the RAD51D protein (p.Val135Glu). 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: 657311). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAD51D protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 | RCV002325594 | SCV002632400 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-27 | criteria provided, single submitter | clinical testing | The p.V135E variant (also known as c.404T>A), located in coding exon 5 of the RAD51D gene, results from a T to A substitution at nucleotide position 404. The valine at codon 135 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is poorly 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 this alteration remains unclear. |