Submissions for variant NM_007294.4(BRCA1):c.1439dup (p.Asn480fs)

dbSNP: rs80357505

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000083022	SCV000299598	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	RCV000047474	SCV000075487	pathogenic	Hereditary breast ovarian cancer syndrome	2023-07-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn480Lysfs*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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 10528853). ClinVar contains an entry for this variant (Variation ID: 54252). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000129465	SCV000184235	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-20	criteria provided, single submitter	clinical testing	The c.1439dupA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of A at nucleotide position 1439, causing a translational frameshift with a predicted alternate stop codon (p.N480Kfs*10). This mutation has been reported in multiple individuals diagnosed with hereditary breast and/or ovarian cancer (van Orsouw NJ et al. J Med Genet. 1999 Oct;36(10):747-53; Bayraktar S et al. Cancer 2012 Mar;118(6):1515-22; Zhang J et al. Breast Cancer Res. Treat. 2016 Aug;158(3):455-62; Sun J et al. Clin Cancer Res, 2017 Oct;23:6113-6119; Li A et al. Gynecol Oncol, 2018 10;151:145-152; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475). Of note, this mutation is also designated as 1558insA in 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000083022	SCV000325069	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	RCV000047474	SCV000588034	pathogenic	Hereditary breast ovarian cancer syndrome	2017-04-20	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000047474	SCV000591331	pathogenic	Hereditary breast ovarian cancer syndrome	2014-04-16	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149701	SCV003838905	pathogenic	Breast and/or ovarian cancer	2021-08-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000083022	SCV004216988	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-03-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129465	SCV004361062	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-16	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known as 1558insA and c.1439_1440insA in the literature. This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 27393621, 29681614, 30078507). 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.
Sharing Clinical Reports Project (SCRP)	RCV000083022	SCV000115096	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000083022	SCV000144093	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing