ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5136G>A (p.Trp1712Ter) (rs80357418)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131830 SCV000186885 pathogenic Hereditary cancer-predisposing syndrome 2018-04-06 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)
Baylor Genetics RCV000475804 SCV000540942 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077600 SCV000145322 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131830 SCV000908990 pathogenic Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077600 SCV000326165 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077600 SCV000300208 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 RCV000481118 SCV000567723 pathogenic not provided 2018-08-08 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5136G>A at the cDNA level and p.Trp1712Ter (W1712X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with hereditary breast and/or ovarian cancer (Ozcelik 2003, van der Hout 2006, Schenkel 2016, Afghahi 2017, Briceno-Balcazar 2017) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048806 SCV000918769 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-06 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5136G>A (p.Trp1712X) 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 allele was found at a frequency of 4.1e-06 in 246144 control chromosomes (gnomAD). The variant, c.5136G>A, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Briceno-Balcazar_2017, Ozcelik_2003, Rebbeck_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000048806 SCV000076819 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1712 (p.Trp1712*) of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with breast and/or ovarian cancer (PMID: 12920083, 16683254, 27836010). This variant is also known as c.5255G>A in the literature. For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048806 SCV000587468 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077600 SCV000109403 pathogenic Breast-ovarian cancer, familial 1 2010-07-12 no assertion criteria provided clinical testing

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