Submissions for variant NM_007294.4(BRCA1):c.3254_3255dup (p.Leu1086fs)

dbSNP: rs80357624

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000143832	SCV000282301	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-22	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	RCV000143832	SCV000325586	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000496892	SCV000591433	pathogenic	Hereditary breast ovarian cancer syndrome		criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771558	SCV000904125	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-06	criteria provided, single submitter	clinical testing	This variant inserts 2 nucleotides 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. This variant has been reported in an individual affected with ovarian cancer (PMID: 24728189). 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.
Ambry Genetics	RCV000771558	SCV001180813	pathogenic	Hereditary cancer-predisposing syndrome	2024-04-10	criteria provided, single submitter	clinical testing	The c.3254_3255dupGA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of GA at nucleotide position 3254, causing a translational frameshift with a predicted alternate stop codon (p.L1086Dfs*2). This mutation has been previously reported in multiple individuals with ovarian cancer (Risch HA et al. Am. J. Hum. Genet. 2001 Mar; 68(3):700-10; Song H et al. Hum. Mol. Genet. 2014 Sep; 23(17):4703-9). Of note, this alteration is also designated as 3374insGA in published 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496892	SCV001579545	pathogenic	Hereditary breast ovarian cancer syndrome	2024-11-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu1086Aspfs*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 ovarian cancer (PMID: 11179017). This variant is also known as 3375insGA. ClinVar contains an entry for this variant (Variation ID: 54806). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002477169	SCV002774307	pathogenic	not provided	2018-06-26	criteria provided, single submitter	clinical testing	This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in an individual with ovarian cancer in the published literature (PMID: 11179017 (2017)). Based on the available information, this variant is classified as pathogenic.
Baylor Genetics	RCV000143832	SCV004217021	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-11-25	criteria provided, single submitter	clinical testing
GeneDx	RCV002477169	SCV005079621	pathogenic	not provided	2023-08-24	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed in individuals with ovarian cancer in published literature (Risch et al., 2001; Song et al., 2014; Lerner-Ellis et al., 2021); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 3375insGA and 3373_3374dup; This variant is associated with the following publications: (PMID: 11179017, 20104584, 31897316, 24728189, 32885271)
Sharing Clinical Reports Project (SCRP)	RCV000143832	SCV000053695	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2010-07-26	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000143832	SCV000144687	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	RCV000496892	SCV000587291	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research