Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000132446 | SCV000187540 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-19 | criteria provided, single submitter | clinical testing | The p.G112D variant (also known as c.335G>A), located in coding exon 4 of the RAD51D gene, results from a G to A substitution at nucleotide position 335. The glycine at codon 112 is replaced by aspartic acid, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000476134 | SCV000551319 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2021-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 112 of the RAD51D protein (p.Gly112Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 142955). 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 disruptive, 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477563 | SCV004220169 | uncertain significance | not provided | 2023-01-19 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |