ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.962G>A (p.Trp321Ter) (rs80357292)

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Total submissions: 13
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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) RCV000031293 SCV000299514 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 RCV000049204 SCV000077217 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp321*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant has been observed in many individuals affected with breast and/or ovarian cancer (PMID: 9333265, 10644434, 15382066, 16287141, 16683254, 22535016). This variant is also known as 1081G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 37712). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000159948 SCV000210095 pathogenic not provided 2018-07-05 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.962G>A at the cDNA level and p.Trp321Ter (W321X) at the protein level. The substitution creates a nonsense variant, changing a Tryptophan to a premature stop codon (TGG>TAG). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 Trp321Ter, previously reported as 1081G>A using alternate nomenclature, has been reported in hereditary breast and/or ovarian cancer as well as in unselected ovarian cancer cases (Shattuck-Eidens 1997, Risch 2001, Claus 2005, Walsh 2011, Belanger 2015, Meric-Bernstam 2016). We consider this variant to be pathogenic.
Ambry Genetics RCV000162891 SCV000213378 pathogenic Hereditary cancer-predisposing syndrome 2019-04-26 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735517 SCV000219201 pathogenic Breast and/or ovarian cancer 2017-01-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159948 SCV000296300 pathogenic not provided 2015-03-04 criteria provided, single submitter clinical testing
GeneKor MSA RCV000239176 SCV000296788 pathogenic not specified 2016-07-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031293 SCV000326474 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000162891 SCV000911645 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031293 SCV000053898 pathogenic Breast-ovarian cancer, familial 1 2012-09-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031293 SCV000143965 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000049204 SCV000587090 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735517 SCV000863655 pathogenic Breast and/or ovarian cancer 2016-02-05 no assertion criteria provided clinical testing

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