ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.220C>T (p.Gln74Ter) (rs80357234)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3DMed Clinical Laboratory Inc RCV000677814 SCV000803974 pathogenic Ovarian cancer 2017-10-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000572393 SCV000665795 pathogenic Hereditary cancer-predisposing syndrome 2017-05-25 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000112044 SCV000144697 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112044 SCV000325289 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) RCV000112044 SCV000299427 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 RCV000414657 SCV000490907 pathogenic not provided 2017-06-09 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.220C>T at the cDNA level and p.Gln74Ter (Q74X) at the protein level. Using alternate nomenclature, this variant has been published as BRCA1 339C>T. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), 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 individuals with hereditary breast and ovarian cancer (Stoppa-Lyonnet 1997, Kiechle 2000, Kwong 2016) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000047758 SCV000698929 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.220C>T (p.Gln74X) 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.Tyr101X, p.Glu143X, p.Ser157X, etc.). This variant is absent in 121250 control chromosomes from ExAC. This variant has been reported in several HBOC affected patients in literature (Stoppa-Lyonnet_1997, Kiechle_2000, Lecarpentier_2012, Bjorkman_2015, Wang_2015, Kwong_2016, Tung_2016, Lang_2017) and clinical databases (UMD, ClinVar). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000047758 SCV000075771 pathogenic Hereditary breast and ovarian cancer syndrome 2018-02-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 74 (p.Gln74*) of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in the literature in individuals affected with breast or ovarian cancer (PMID: 9150149). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047758 SCV000587040 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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