ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.620A>G (p.His207Arg) (rs587781921)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130270 SCV000185115 uncertain significance Hereditary cancer-predisposing syndrome 2014-02-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000130270 SCV000909448 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-12 criteria provided, single submitter clinical testing
GeneDx RCV000236462 SCV000293303 uncertain significance not provided 2015-10-27 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.620A>G at the cDNA level, p.His207Arg (H207R) at the protein level, and results in the change of a Histidine to a Arginine (CAT>CGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant 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 Histidine and Arginine share similar properties, this is considered a conservative amino acid substitution. RAD51C His207Arg occurs at a position that is conserved in mammals and is located within the ATPase domain (Kim 2011). 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 His207Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000470632 SCV000550185 uncertain significance Fanconi anemia, complementation group O 2018-09-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 207 of the RAD51C protein (p.His207Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (rs587781921, ExAC no frequency). This variant has been reported in an individual affected with ovarian cancer (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 141663). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The arginine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. 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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