ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1356_1357AG[2] (p.Glu453_Ser454insTer) (rs80357969)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131838 SCV000186893 pathogenic Hereditary cancer-predisposing syndrome 2017-10-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion),Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000030987 SCV000144066 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131838 SCV000688334 pathogenic Hereditary cancer-predisposing syndrome 2017-07-17 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000030987 SCV000325047 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000030987 SCV000564354 pathogenic Breast-ovarian cancer, familial 1 2015-01-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000456126 SCV000591325 pathogenic Hereditary breast and ovarian cancer syndrome 2014-08-08 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000030987 SCV000299586 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000047440 SCV000210012 pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1360_1361delAGAG>- at the cDNA level and p.Ser454Ter (S454X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (AGT>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This BRCA1 variant, also denoted 1479delAG using alternate nomenclature, has been reported in association with breast and ovarian cancer (Ottini 2000, Zhang 2011) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000456126 SCV000698854 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-09 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1360_1361delAG (p.Ser454Terfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121340 (1/60670), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant of interest was reported in multiple affected individuals via publications. In addition, multiple clinical diagnostic laboratories/databases cite the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Invitae RCV000456126 SCV000075453 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser454*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80357969, ExAC 0.003%). This variant has been observed in several individuals with personal or family history of breast and/or ovarian cancer (PMID: 10528853, 22874498, 26681312, 26219728). This variant is also known as 1479delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 37406). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000456126 SCV000839286 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000047440 SCV000600249 pathogenic not provided 2017-02-12 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000456126 SCV000587124 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000030987 SCV000053579 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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