ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4508C>A (p.Ser1503Ter) (rs80357437)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129157 SCV000183883 pathogenic Hereditary cancer-predisposing syndrome 2013-01-08 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112351 SCV000145111 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112351 SCV000325990 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112351 SCV000785411 pathogenic Breast-ovarian cancer, familial 1 2017-07-26 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112351 SCV000744614 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496782 SCV000591524 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000112351 SCV000733610 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112351 SCV000300131 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 RCV000657616 SCV000779358 pathogenic not provided 2016-10-18 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4508C>A at the cDNA level and p.Ser1503Ter (S1503X) 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 reported as BRCA1 4627C>A using alternate nomenclature, has been observed in multiple breast/ovarian cancer families and is considered pathogenic (Liede 2002, Rashid 2006, van der Hout 2006, Thomassen 2008).
Integrated Genetics/Laboratory Corporation of America RCV000496782 SCV000918705 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-13 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4508C>A (p.Ser1503X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Glu1694X, p.Gln1747X and p.Ser1796X). This variant was found in 2/246080 control chromosomes (gnomAD) at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). This variant has been found in several triple negative breast cancer patients from Pakistan (Liede_2002, Rashid_2006, Rashid_2016). Multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112351 SCV000296443 pathogenic Breast-ovarian cancer, familial 1 2016-03-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657616 SCV000887700 pathogenic not provided 2016-03-19 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496782 SCV000587405 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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