ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.890T>C (p.Leu297Pro) (rs143026267)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166479 SCV000217277 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000166479 SCV000686401 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-18 criteria provided, single submitter clinical testing
Counsyl RCV000409000 SCV000489981 uncertain significance Fanconi anemia, complementation group O 2016-09-06 criteria provided, single submitter clinical testing
Counsyl RCV000410543 SCV000489982 uncertain significance Breast-ovarian cancer, familial 3 2016-09-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000657146 SCV000231811 uncertain significance not provided 2014-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000657146 SCV000571427 uncertain significance not provided 2018-09-11 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.890T>C at the cDNA level, p.Leu297Pro (L297P) at the protein level, and results in the change of a Leucine to a Proline (CTT>CCT). This variant has been observed in an individual with a personal history of a Lynch syndrome-associated cancer and/or polyps as well as in an individual with gallbladder cancer (Yurgelun 2015, Shindo 2017). RAD51C Leu297Pro was observed at an allele frequency of 0.05% (13/24,012) in individuals of African ancestry in large population cohorts (Lek 2016). Since Leucine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. RAD51C Leu297Pro is located in the region of interaction with RAD51B, RAD51D, and XRCC3 (Miller 2004). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether RAD51C Leu297Pro is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000409000 SCV000550210 uncertain significance Fanconi anemia, complementation group O 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 297 of the RAD51C protein (p.Leu297Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs143026267, ExAC 0.06%). This variant has been observed in an individual affected with gall bladder adenocarcinoma and an individual undergoing testing for Lynch syndrome (PMID: 28767289, 25980754). ClinVar contains an entry for this variant (Variation ID: 186828). 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.
PreventionGenetics RCV000657146 SCV000807182 uncertain significance not provided 2017-01-10 criteria provided, single submitter clinical testing

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