ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2309C>A (p.Ser770Ter) (rs80357063)

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Total submissions: 11
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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) RCV000077513 SCV000299743 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 RCV000047791 SCV000075804 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser770*) 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 in individuals affected with breast and ovarian cancer (PMID: 9808526, 22006311, 10866029, 25452441), as well as in individuals in the Breast Cancer Information Core database (PMID: 10923033). This variant is also known as 2428C>A in the literature. ClinVar contains an entry for this variant (Variation ID: 54527). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000047791 SCV000271315 pathogenic Hereditary breast and ovarian cancer syndrome 2015-07-29 criteria provided, single submitter clinical testing The p.Ser770X variant has been reported in at least 8 individuals with BRCA1-ass ociated cancers (Santarosa 1998, Walsh 2014, Couch 2015, Breast Cancer Informati on Core) and was absent from large population studies. This nonsense variant lea ds to a premature termination codon at position 770, which is predicted to lead to a truncated or absent protein. Heterozygous loss of BRCA1 function is an esta blished disease mechanism in hereditary breast and ovarian cancer (HBOC). In add ition, this variant was classified as Pathogenic on September 8, 2016 by the Cli nGen-approved ENIGMA expert panel (ClinVar SCV000299743.2). In summary, the p.S er770X variant meets criteria to be classified as pathogenic for HBOC in an auto somal dominant manner based upon the predicted impact to the protein, presence i n affected individuals, and absence from controls.
Ambry Genetics RCV000222520 SCV000273967 pathogenic Hereditary cancer-predisposing syndrome 2017-08-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077513 SCV000296405 pathogenic Breast-ovarian cancer, familial 1 2015-11-05 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077513 SCV000325319 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000445000 SCV000516786 pathogenic not provided 2018-09-06 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2309C>A at the cDNA level and p.Ser770Ter (S770X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as 2428C>A using alternate nomenclature, has been observed in association with Hereditary Breast and Ovarian Cancer syndrome (Santarosa 1998, Marroni 2004, Miolo 2009, Walsh 2011). This variant is considered pathogenic.
Counsyl RCV000077513 SCV000677641 pathogenic Breast-ovarian cancer, familial 1 2017-01-03 criteria provided, single submitter clinical testing
Color RCV000222520 SCV000683025 pathogenic Hereditary cancer-predisposing syndrome 2015-04-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077513 SCV000109313 pathogenic Breast-ovarian cancer, familial 1 2011-08-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077513 SCV000144374 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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