ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2800C>T (p.Gln934Ter) (rs80357223)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA1) RCV000077528 SCV000144550 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000579514 SCV000683063 pathogenic Hereditary cancer-predisposing syndrome 2017-01-05 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077528 SCV000325465 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077528 SCV000744645 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077528 SCV000733634 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077528 SCV000282290 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000236201 SCV000292514 pathogenic not provided 2016-09-22 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2800C>T at the cDNA level and p.Gln934Ter (Q934X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA1 2919C>T using alternate nomenclature, has been published as a Japanese pathogenic founder variant and has been observed in several breast and/or ovarian cancer families (Kashima 2000, Sekine 2001, Sugano 2008, Hirotsu 2015, Sakamoto 2016). We consider it to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000047973 SCV000916748 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-12 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2800C>T (p.Gln934X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 245896 control chromosomes. c.2800C>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer mainly occurring in the Japanese population, where it appeared to be a founder mutation (E.G. Sekine 2001). These data indicate that the variant is very likely to be associated with disease. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000047973 SCV000075986 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 934 (p.Gln934*) of 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 individuals and families affected with breast and/or ovarian cancer, and has been suggested to be a founder mutation in the Japanese population (PMID: 10804288, 11595708, 25802882, 19016756, 11149425, 18159056). It is also known as 2919C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54683). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000047973 SCV000839266 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077528 SCV000109329 pathogenic Breast-ovarian cancer, familial 1 2011-12-13 no assertion criteria provided clinical testing

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