ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3895C>T (p.Gln1299Ter) (rs80357038)

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Total submissions: 10
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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) RCV000112209 SCV000300038 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131813 SCV000186868 pathogenic Hereditary cancer-predisposing syndrome 2013-09-19 criteria provided, single submitter clinical testing The p.Q1299X pathogenic mutation (also known as c.3895C>T and 4014C>T) is located in coding exon 9 of the BRCA1 gene. This alteration results from a C to T substitution at nucleotide position 3895.This changes the amino acid from a glutamine to a stop codon within coding exon 9. This mutation has been detected in numerous Korean breast and ovarian cancer families (Kang HC et al. Hum Mutat. 2002;20(3):235, Kim H et al. Breast Cancer Res Treat. 2012;134(3):1315-26). In addition to the clinical data presented in the literature, and since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112209 SCV000325780 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000112209 SCV000489514 likely pathogenic Breast-ovarian cancer, familial 1 2016-10-18 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000496298 SCV000588050 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508684 SCV000605859 pathogenic not provided 2017-04-17 criteria provided, single submitter clinical testing
GeneDx RCV000508684 SCV000779329 pathogenic not provided 2018-11-21 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3895C>T at the cDNA level and p.Gln1299Ter (Q1299X) 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 reported as BRCA1 4014C>T using alternate nomenclature, has been reported in several Korean families with breast and/or ovarian cancer (Kang 2002, Shin 2016, Choi 2018). Based on currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000496298 SCV001582764 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1299*) in 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 one individual affected with breast cancer and two individuals affected with ovarian cancer from a single family (PMID: 12204006). ClinVar contains an entry for this variant (Variation ID: 55040). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112209 SCV000144911 pathogenic Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496298 SCV000587355 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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