Submissions for variant NM_007294.4(BRCA1):c.3296del (p.Pro1099fs)

dbSNP: rs80357815

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112052	SCV000299912	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112052	SCV000325602	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000564656	SCV000660994	pathogenic	Hereditary cancer-predisposing syndrome	2022-01-19	criteria provided, single submitter	clinical testing	The c.3296delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 3296, causing a translational frameshift with a predicted alternate stop codon (p.P1099Lfs*10). This alteration has been reported in individuals with familial breast and/or ovarian cancer in multiple populations (Kim H et al. Breast Cancer Res Treat, 2012 Aug;134:1315-26; Koczkowska M et al. Cancers (Basel), 2018 Nov;10; Lim MC et al. J Cancer Res Clin Oncol, 2009 Nov;135:1593-9; Seong MW et al. Clin Genet, 2009 Aug;76:152-60; Southey MC et al. Br. J. Cancer, 1999 Jan;79:34-9; Eoh KJ et al. Cancer Res Treat, 2018 Jul;50:917-925; Kang E et al. Breast Cancer Res Treat, 2015 May;151:157-68; Cao WM et al. BMC Cancer, 2016 Feb;16:64; Li A et al. Gynecol Oncol, 2018 10;151:145-152). Of note, this alteration is also designated as 3415delC in published literature. In addition to the information 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	RCV000496407	SCV001582262	pathogenic	Hereditary breast ovarian cancer syndrome	2023-04-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54824). This variant is also known as 3415delC. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro1099Leufs*10) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584).
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003237430	SCV002009452	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000564656	SCV002053478	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-07	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and 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 detected in at least 7 individuals affected with breast and ovarian cancer (PMID: 10498392, 19499246, 22798144, 29020732, 29673794, 30207098, 33850850) and reported in a breast cancer case-control meta-analysis in 2/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_000654). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV000112052	SCV004212707	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-10-17	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV003237430	SCV005196944	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112052	SCV000144705	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496407	SCV000587295	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research