ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.1090A>G (p.Ser364Gly)

gnomAD frequency: 0.00003  dbSNP: rs587782565
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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 RCV000131788 SCV000186837 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-14 criteria provided, single submitter clinical testing The p.S364G variant (also known as c.1090A>G), located in coding exon 9 of the RAD51C gene, results from an A to G substitution at nucleotide position 1090. The serine at codon 364 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a high-risk breast and/or ovarian cancer family (Lu W et al. Fam. Cancer, 2012 Sep;11:381-5). Another study detected this alteration in 0/3429 patients with invasive epithelial ovarian cancer and 1/2772 unaffected controls (Song H et al. J. Clin. Oncol., 2015 Sep;33:2901-7). This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000232947 SCV000291211 uncertain significance Fanconi anemia complementation group O 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 364 of the RAD51C protein (p.Ser364Gly). This variant is present in population databases (rs587782565, gnomAD 0.002%). This missense change has been observed in individual(s) with breast cancer (PMID: 22476429, 26261251). ClinVar contains an entry for this variant (Variation ID: 142585). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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, LLC DBA Color Health RCV000131788 SCV000292215 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-16 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 364 of the RAD51C 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 performed for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 22476429), but also in unaffected individuals (PMID 26261251; https://whi.color.com/variant/17-56811542-A-G.). This variant has been identified in 2/281650 chromosomes 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.
GeneDx RCV000482155 SCV000572601 uncertain significance not provided 2024-06-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in an individual with a personal history of breast cancer and a family history of breast and/or ovarian cancer (PMID: 22476429); Published functional studies demonstrate normal in vitro homology-directed repair (HDR) activity (PMID: 37253112); This variant is associated with the following publications: (PMID: 34480478, 26261251, 25470109, 26406419, 23117857, 34923718, 14704354, 22476429, 37253112)
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano RCV001270237 SCV001364368 likely pathogenic Premature ovarian failure 2020-03-02 criteria provided, single submitter research
Baylor Genetics RCV003462023 SCV004207956 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2023-08-30 criteria provided, single submitter clinical testing

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