Submissions for variant NM_058216.3(RAD51C):c.955C>T (p.Arg319Ter)

gnomAD frequency: 0.00001  dbSNP: rs587781287

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000128973	SCV000172859	pathogenic	Hereditary cancer-predisposing syndrome	2024-09-24	criteria provided, single submitter	clinical testing	The p.R319* pathogenic mutation (also known as c.955C>T), located in coding exon 7 of the RAD51C gene, results from a C to T substitution at nucleotide position 955. This changes the amino acid from an arginine to a stop codon within coding exon 7. This mutation has been reported in multiple individuals with personal and/or family histories of breast and/or ovarian cancer (Loveday C et al. Nat. Genet., 2012 Apr;44:475-6; author reply 476; Couch FJ et al. J Clin Oncol, 2015 Feb;33:304-11; Song H et al. J Clin Oncol, 2015 Sep;33:2901-7; Norquist BM et al. JAMA Oncol, 2016 Apr;2:482-90; Kraus C et al. Int J Cancer, 2017 Jan;140:95-102; Schoolmeester JK et al. Hum. Pathol., 2017 12;70:14-26; Hoyer J et al. BMC Cancer, 2018 Sep;18:926; Dorling et al. N Engl J Med. 2021 02;384:428-439). In addition to the clinical data presented in the literature, 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	RCV000230603	SCV000291256	pathogenic	Fanconi anemia complementation group O	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg319*) 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 present in population databases (rs587781287, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 22538716, 25452441, 26261251). ClinVar contains an entry for this variant (Variation ID: 140799). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000128973	SCV000537646	pathogenic	Hereditary cancer-predisposing syndrome	2021-01-25	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 7 of the RAD51C gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast or ovarian cancer (PMID: 22538716, 25452441, 26261251, 26720728, 27616075, 28709830, 32359370). This variant has been identified in 2/251282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
GeneDx	RCV000483841	SCV000566619	pathogenic	not provided	2023-10-02	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25470109, 24763289, 22538716, 26720728, 26261251, 25452441, 27616075, 28709830, 30257646, 29922827, 32359370, 34923718, 28888541, 33804961, 33471991, 34326862, 36169650)
Genetic Services Laboratory, University of Chicago	RCV000501924	SCV000596689	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2016-12-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128973	SCV002530037	pathogenic	Hereditary cancer-predisposing syndrome	2020-10-27	criteria provided, single submitter	curation
Baylor Genetics	RCV000501924	SCV004207950	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2023-09-06	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000501924	SCV004931947	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-01-03	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Fulgent Genetics, Fulgent Genetics	RCV005016428	SCV005649747	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2024-05-03	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000483841	SCV001977630	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000483841	SCV001979490	pathogenic	not provided		no assertion criteria provided	clinical testing