Submissions for variant NM_058216.3(RAD51C):c.905_908dup (p.Ser304fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV004442593	SCV004930919	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-02-13	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005104642	SCV005840021	likely pathogenic	Fanconi anemia complementation group O	2024-12-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser304Glyfs*45) in the RAD51C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acid(s) of the RAD51C protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 3148699). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the nuclear localization signal (NLS) of the RAD51C protein, which is important for proper localization and function of the RAD51C protein (PMID:12966089). While functional studies have not been performed to directly test the effect of this variant on RAD51C protein function, this suggests that disruption of this region of the protein is causative of disease. 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.