ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.395C>G (p.Thr132Arg) (rs730881930)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160922 SCV000211626 uncertain significance not provided 2016-11-29 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.395C>G at the cDNA level, p.Thr132Arg (T132R) at the protein level, and results in the change of a Threonine to an Arginine (ACA>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Thr132Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Threonine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. RAD51C Thr132Arg occurs at a position that is conserved across species and is located within an ATPase motif and the region of interaction with RAD51B, RAD51D, and XRCC3 (French 2003, Miller 2004). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether RAD51C Thr132Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000206110 SCV000261074 uncertain significance Fanconi anemia, complementation group O 2019-10-06 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 132 of the RAD51C protein (p.Thr132Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. 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: 182834). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Ambry Genetics RCV000218584 SCV000276270 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000218584 SCV000909440 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-24 criteria provided, single submitter clinical testing

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