Submissions for variant NM_007294.4(BRCA1):c.2702_2703del (p.Thr900_Phe901insTer)

dbSNP: rs80357899

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111921	SCV000299815	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	RCV000111921	SCV000325437	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Pathology and Molecular Medicine, Queen's University	RCV000496890	SCV000588041	pathogenic	Hereditary breast ovarian cancer syndrome	2017-04-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496890	SCV001586488	pathogenic	Hereditary breast ovarian cancer syndrome	2021-08-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe901*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ovarian cancer (PMID: 11179017, 28541631). This variant is also known as c.2819delTT in the literature. ClinVar contains an entry for this variant (Variation ID: 54653). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002426607	SCV002742144	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-27	criteria provided, single submitter	clinical testing	The c.2702_2703delTT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2702 to 2703, causing a translational frameshift with a predicted alternate stop codon (p.F901*). This alteration has been identified in individuals diagnosed with breast and/or ovarian cancer (Risch HA et al. Am J Hum Genet, 2001 Mar;68:700-10; Zhao Q et al. J Gynecol Oncol, 2017 Jul;28:e39; Shao D et al. Cancer Sci, 2020 Feb;111:647-657). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). Of note, this alteration is also known as 2819delTT in published literature. 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.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111921	SCV000144517	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496890	SCV000587248	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research