Submissions for variant NM_058216.3(RAD51C):c.858_861dup (p.Thr288fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV004442573	SCV004930879	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-01-17	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics	RCV004661831	SCV005159498	pathogenic	Hereditary cancer-predisposing syndrome	2024-04-10	criteria provided, single submitter	clinical testing	The c.858_861dupGACA pathogenic mutation, located in coding exon 6 of the RAD51C gene, results from a duplication of GACA at nucleotide position 858, causing a translational frameshift with a predicted alternate stop codon (p.T288Dfs*5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005104641	SCV005758852	pathogenic	Fanconi anemia complementation group O	2024-06-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr288Aspfs*5) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). 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. For these reasons, this variant has been classified as Pathogenic.