Submissions for variant NM_058216.3(RAD51C):c.964del (p.Arg322fs) (rs1555603056)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color	RCV000584392	SCV000691294	likely pathogenic	Hereditary cancer-predisposing syndrome	2018-08-22	criteria provided, single submitter	clinical testing
Invitae	RCV000701832	SCV000830651	likely pathogenic	Fanconi anemia, complementation group O	2018-02-05	criteria provided, single submitter	clinical testing	This sequence change results in a premature translational stop signal in the RAD51C gene (p.Arg322Glyfs*42). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acids of the RAD51C protein. 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. While the effect of this particular sequence change on RAD51C function has not been tested, the C-terminal region of RAD51C is known to contain a nuclear localization signal, and the deletion of the 11 C-terminal residues leads to cellular mislocalization of the protein, as well as reduced mitomycin C resistance compared to the wild-type protein (PMID: 12966089). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.