ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4612C>T (p.Gln1538Ter) (rs80356992)

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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) RCV000077579 SCV000300145 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 RCV000048606 SCV000076619 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1538 (p.Gln1538*). 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 with breast and/or ovarian cancer (PMID: 9452076, 11920621, 25151137). This variant is also known as 4731C>T in the literature. For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077579 SCV000326009 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000420125 SCV000516967 pathogenic not provided 2018-08-13 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4612C>T at the cDNA level and p.Gln1538Ter (Q1538X) 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 published as BRCA1 4731C>T using alternate nomenclature, has been observed in individuals with personal and/or family histories of breast and ovarian cancer (Tartaglini 1998, De Leon Matsuda 2002, Young 2009, Guan 2015) and is considered pathogenic.
Ambry Genetics RCV000510121 SCV000607974 pathogenic Hereditary cancer-predisposing syndrome 2016-07-25 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000420125 SCV001133591 pathogenic not provided 2019-05-02 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient in literature, and not found in general population data.
Sharing Clinical Reports Project (SCRP) RCV000077579 SCV000109382 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077579 SCV000145129 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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