ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5154G>A (p.Trp1718Ter) (rs80357239)

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Total submissions: 8
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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) RCV000077604 SCV000300213 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 RCV000212195 SCV000210203 pathogenic not provided 2014-03-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.5154G>A at the cDNA level and p.Trp1718Ter (W1718X) at the protein level. The substitution creates a nonsense variant, changing a Tryptophan to a premature stop codon (TGG>TGA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as 5273G>A using alternate nomenclature, has been reported in association with breast and/or ovarian cancer (Shattuck-Eidens 1997, Cao 2013). We therefore consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077604 SCV000326185 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Genologica Medica RCV000077604 SCV000577936 pathogenic Breast-ovarian cancer, familial 1 2017-01-01 criteria provided, single submitter clinical testing
Color RCV000580491 SCV000683265 pathogenic Hereditary cancer-predisposing syndrome 2016-12-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779910 SCV000916821 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-29 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5154G>A (p.Trp1718X) 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 245724 control chromosomes (gonmAD) and has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Cao_2016, Li_2018, Jimenez _2013). These data indicate that the variant is very likely to be associated with disease. Four 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.
Sharing Clinical Reports Project (SCRP) RCV000077604 SCV000109407 pathogenic Breast-ovarian cancer, familial 1 2013-05-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077604 SCV000145361 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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