Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000470385 | SCV000551347 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-06-04 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 131 of the RAD51D protein (p.Asn131Ser). 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: 410554). 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. |
| Color Diagnostics, |
RCV000771343 | SCV000903625 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-25 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 131 of the RAD51D protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RAD51D-related disorders in the literature, but has been reported in two unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID RAD51D_000150). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000771343 | SCV001183077 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | The p.N131S variant (also known as c.392A>G), located in coding exon 5 of the RAD51D gene, results from an A to G substitution at nucleotide position 392. The asparagine at codon 131 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well 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. |
| Sema4, |
RCV000771343 | SCV002534811 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-30 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV000470385 | SCV004208090 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2023-10-06 | criteria provided, single submitter | clinical testing |