ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.3G>A (p.Met1Ile) (rs769053886)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216075 SCV000274466 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,Other data supporting benign classification
Color RCV000216075 SCV000686349 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-25 criteria provided, single submitter clinical testing
GeneDx RCV000579223 SCV000680878 uncertain significance not provided 2018-09-20 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.3G>A at the cDNA level and alters the initiator Methionine codon.The resultant protein would be described as “p.Met1?” to signify that it is not known if the loss of Met1 prevents allprotein translation or if an abnormal protein is produced using an alternate Methionine codon. This variant has not, toour knowledge, been published in the literature as pathogenic or benign. According to French et al. (2003), there isanother Methionine 10 codons downstream that could potentially function as an initiation codon; therefore, it is possiblethat some functional protein is produced. Based on currently available evidence, it is unclear whether RAD51Cc.3G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000648266 SCV000770080 uncertain significance Fanconi anemia, complementation group O 2018-09-20 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the RAD51C mRNA. The next in-frame methionine is located at codon 10. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 230796). An experimental study has shown that the RAD51C protein created from the downstream methionine at codon 10 (p.Met10) is biologically active, exhibiting wild-type activity in complementing mitomycin C sensitivity in a RAD51C-deficient cell line (PMID: 12966089). Based on these results, the impact of this variant on RAD51C protein function 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.
Mendelics RCV000709499 SCV000839323 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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