Submissions for variant NM_007294.4(BRCA1):c.5102_5103del (p.Leu1701fs)

dbSNP: rs80357608

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)	RCV000077596	SCV000300200	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048795	SCV000076808	pathogenic	Hereditary breast ovarian cancer syndrome	2021-03-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been observed in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 12204006, 16905680, 29446198). ClinVar contains an entry for this variant (Variation ID: 55401). This variant is present in population databases (rs80357608, ExAC 0.01%). This sequence change creates a premature translational stop signal (p.Leu1701Glnfs*14) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000077596	SCV000326155	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336192	SCV002642477	pathogenic	Hereditary cancer-predisposing syndrome	2020-03-31	criteria provided, single submitter	clinical testing	The c.5102_5103delTG pathogenic mutation, located in coding exon 16 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 5102 to 5103, causing a translational frameshift with a predicted alternate stop codon (p.L1701Qfs*14). This variant has been identified in hereditary breast and ovarian cancer families world wide (Kang HC et al. Hum. Mutat., 2002 Sep;20:235; Simard J et al. J. Med. Genet., 2007 Feb;44:107-21; Cavallone L et al. Fam. Cancer, 2010 Dec;9:507-17; Kim H et al. Breast Cancer Res. Treat., 2012 Aug;134:1315-26; Belanger MH et al. J Ovarian Res, 2015 Mar;8:1; Briceño-Balcázar I et al. Colomb. Med., 2017 Jun;48:58-63; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620; Ryu JM et al. Breast Cancer Res. Treat., 2019 Jan;173:385-395; Kwon BS et al. Cancer Res Treat, 2019 Jul;51:941-950). Of note, this alteration is also designated as 5221delTG in the published 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.
Sharing Clinical Reports Project (SCRP)	RCV000077596	SCV000109399	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2006-10-05	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077596	SCV000145314	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000048795	SCV000587463	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735489	SCV000863626	pathogenic	Breast and/or ovarian cancer	2011-10-10	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357324	SCV001552766	uncertain significance	not provided		no assertion criteria provided	clinical testing
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001572614	SCV001775484	pathogenic	Breast carcinoma	2021-08-08	no assertion criteria provided	clinical testing