ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.158C>G (p.Ser53Cys)

dbSNP: rs876659265
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221232 SCV000275518 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-18 criteria provided, single submitter clinical testing The p.S53C variant (also known as c.158C>G), located in coding exon 2 of the RAD51C gene, results from a C to G substitution at nucleotide position 158. The serine at codon 53 is replaced by cysteine, an amino acid with dissimilar properties. In a homology-directed DNA repair (HDR) assay, this alteration showed a functionally indeterminant read-out (Hu C et al. Cancer Res, 2023 Aug;83:2557-2571). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000221232 SCV000686328 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000648232 SCV000770046 uncertain significance Fanconi anemia complementation group O 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 53 of the RAD51C protein (p.Ser53Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 231616). 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 expected to disrupt RAD51C protein function with a positive 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.
GeneDx RCV001753663 SCV001996006 uncertain significance not provided 2024-06-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individual(s) with breast cancer (PMID: 29522266); Published functional studies demonstrate no impact on homology-directed repair activity (PMID: 37253112); This variant is associated with the following publications: (PMID: 29522266, 37253112)
Fulgent Genetics, Fulgent Genetics RCV002503871 SCV002815421 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O 2021-11-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV003469038 SCV004207947 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2023-09-07 criteria provided, single submitter clinical testing

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