ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.451G>A (p.Val151Met) (rs753912045)

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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 RCV000218803 SCV000278520 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000218803 SCV000686353 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-10 criteria provided, single submitter clinical testing
GeneDx RCV000657007 SCV000566222 uncertain significance not provided 2017-06-27 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.451G>A at the cDNA level, p.Val151Met (V151M) 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. RAD51C Val151Met was observed at an allele frequency of 0.018% (3/16,512) in individuals of South Asian ancestry in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. RAD51C Val151Met occurs at a position where amino acids with properties similar to Valine are tolerated across species and is not located in a known functional domain. 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 RAD51C Val151Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Genetic Services Laboratory, University of Chicago RCV000486372 SCV000596688 uncertain significance not specified 2015-11-10 criteria provided, single submitter clinical testing
Invitae RCV000576264 SCV000676960 uncertain significance Fanconi anemia, complementation group O 2018-11-25 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 151 of the RAD51C protein (p.Val151Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs753912045, ExAC 0.02%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 234035). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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