Submissions for variant NM_007294.4(BRCA1):c.1086_1087del (p.Asn363fs)

dbSNP: rs80357897

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111543	SCV000299534	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	RCV000111543	SCV000324950	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496894	SCV001588447	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn363Serfs*2) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with personal and family history of breast cancer and/or ovarian cancer (PMID: 9667259, 28324225). This variant is also known as 1205delGA. ClinVar contains an entry for this variant (Variation ID: 54123). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002426598	SCV002728616	pathogenic	Hereditary cancer-predisposing syndrome	2022-10-18	criteria provided, single submitter	clinical testing	The c.1086_1087delGA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 1086 to 1087, causing a translational frameshift with a predicted alternate stop codon (p.N363Sfs*2). This mutation has been reported in multiple individuals with features of hereditary breast and ovarian cancer (HBOC) syndrome (Frank TS et al. J Clin Oncol, 1998 Jul;16:2417-25; Meisel C et al. Arch Gynecol Obstet, 2017 May;295:1227-1238; Silvestri V et al. JAMA Oncol, 2020 08;6:1218-1230). Of note, this alteration is also designated as 1205delGA in the literature. 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.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111543	SCV000144002	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1997-02-15	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496894	SCV000587102	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research