ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.541G>A (p.Val181Met)

gnomAD frequency: 0.00001  dbSNP: rs876658678
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218763 SCV000274252 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-22 criteria provided, single submitter clinical testing The p.V181M variant (also known as c.541G>A), located in coding exon 6 of the RAD51D gene, results from a G to A substitution at nucleotide position 541. The valine at codon 181 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not 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.
GeneDx RCV000484139 SCV000571723 uncertain significance not provided 2016-09-19 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.541G>A at the cDNA level, p.Val181Met (V181M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Val181Met was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. RAD51D Val181Met occurs at a position that is not conserved and is located in the ATPase domain (Kim 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether RAD51D Val181Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000694399 SCV000822843 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2023-08-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 181 of the RAD51D protein (p.Val181Met). 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: 230636). 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.
Baylor Genetics RCV000694399 SCV004200388 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2023-08-07 criteria provided, single submitter clinical testing

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