ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3916_3917del (p.Leu1306fs) (rs80357678)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083200 SCV000300043 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048379 SCV000076392 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1306Aspfs*23) 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 reported in the literature individuals with a BRCA1-related disease (PMID: 8808710, 20373018, 26187060, 25452441). This variant is also known as 4035delTT (L1306fs) in the literature. ClinVar contains an entry for this variant (Variation ID: 55049). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083200 SCV000325789 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563706 SCV000664800 pathogenic Hereditary cancer-predisposing syndrome 2017-04-26 criteria provided, single submitter clinical testing The c.3916_3917delTT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 3916 to 3917, causing a translational frameshift with a predicted alternate stop codon (p.L1306Dfs*23). This alteration has been reported in individuals with triple negative breast cancer and familial breast cancer (Couch FJ et al. J. Clin. Oncol. 2015 Feb;33:304-11; Zhang J et al. Breast Cancer Res. Treat. 2012 Apr;132:421-8​; Kwong A et al. J. Med. Genet. 2016 Jan;53:15-23; Kim YC et al. Oncotarget 2016 Feb;7:9600-12; Fernandes GC et al. Oncotarget 2016 Dec;7:80465-80481). This mutation has also been reported to co-occur with mutations in BRCA2 (Zuradelli M et al. Breast Cancer Res. Treat. 2010 Nov;124:251-8; Rebbeck TR et al. Breast Cancer Res. 2016 Nov;18:112). 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.
Mendelics RCV000048379 SCV000839244 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284293 SCV001469998 pathogenic not provided 2019-10-04 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Research and Development, ARUP Laboratories RCV001662199 SCV001878592 pathogenic Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2013-12-01 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000083200 SCV000115274 pathogenic Breast-ovarian cancer, familial 1 2012-10-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083200 SCV000144916 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000083200 SCV000583511 likely pathogenic Breast-ovarian cancer, familial 1 2016-11-02 no assertion criteria provided clinical testing This variant has previously been described as disease-causing for breast-ovarian cancer by De Benedetti et al. in 1996 and Zuradelli et al. in 2010 (HGMD professional 2015.3-PMID: 8808710 and 20373018). This variant has not been described by the Exome Sequencing Project, 1000 genome and ExAC. This variant has not been previously detected by CentoMD. However, this variant is been reported in two clinical entries in ClinVar as pathogenic. The patient presented with right breast cancer at 17 years of age, later she was detected with ovarian cancer at the age of 49 years which had metastasized to liver, peritoneum and brain. She passed away at the age of 56 years. Her two daughters of age 30 years and 26 years were also diagnosed to be heterozygous for the same mutation.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048379 SCV000587358 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Medical Genetics Laboratory, Umraniye Training and Research Hospital,University of Health Sciences RCV001554262 SCV001774860 pathogenic Ovarian carcinoma 2021-08-09 no assertion criteria provided clinical testing

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