ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4609C>T (p.Gln1537Ter) (rs80357229)

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Total submissions: 11
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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) RCV000112363 SCV000300142 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112363 SCV000326007 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000479214 SCV000564740 pathogenic not provided 2018-05-24 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4609C>T at the cDNA level and p.Gln1537Ter (Q1537X) at the protein level. 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, previously reported as c.4728C>T, has been observed in association with breast and/or ovarian cancer (Ozcelik 2003, Yassaee 2016) and is considered pathogenic.
Ambry Genetics RCV000509797 SCV000608084 pathogenic Hereditary cancer-predisposing syndrome 2018-05-15 criteria provided, single submitter clinical testing The p.Q1537* pathogenic mutation (also known as c.4609C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4609. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This pathogenic mutation, designated as 4728C>T, has been reported in one individual diagnosed with invasive breast cancer (Ozcelik H et al. J Med Genet. 2003 Aug;40(8):e91). This mutation has also been identified in a patient of Iranian ethnicity with both a personal and family history of breast and/or ovarian cancers (Yassaee VR et al. Asian Pac J Cancer Prev. 2016;17(S3):149-53). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000112363 SCV000746293 pathogenic Breast-ovarian cancer, familial 1 2017-12-03 criteria provided, single submitter clinical testing
Invitae RCV000496357 SCV001588703 pathogenic Hereditary breast and ovarian cancer syndrome 2020-02-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1537*) 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 observed in individual(s) affected with breast cancer and ovarian (PMID: 12920083, 27165220, 30078507). This variant is also known as p.Q1537X (c.4728C>T) in the literature. ClinVar contains an entry for this variant (Variation ID: 55237). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research and Development, ARUP Laboratories RCV001663909 SCV001877250 pathogenic Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2013-12-01 criteria provided, single submitter curation
Breast Cancer Information Core (BIC) (BRCA1) RCV000112363 SCV000145127 pathogenic Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112363 SCV000297613 pathogenic Breast-ovarian cancer, familial 1 2008-02-08 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496357 SCV000587412 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000479214 SCV001552263 uncertain significance not provided no assertion criteria provided clinical testing

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