ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1612C>T (p.Gln538Ter)

dbSNP: rs80356893
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Total submissions: 13
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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) RCV000077492 SCV000299626 pathogenic Breast-ovarian cancer, familial, susceptibility to, 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 RCV000077492 SCV000325108 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507406 SCV000602689 pathogenic not specified 2016-10-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569665 SCV000665136 pathogenic Hereditary cancer-predisposing syndrome 2017-06-01 criteria provided, single submitter clinical testing The p.Q538* pathogenic mutation (also known as c.1612C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 1612. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This mutation has been reported in numerous individuals with early onset breast cancer and/or familial breast and ovarian cancer (Ahn SH et al. Cancer Lett. 2007 Jan;245:90-5; Kluska A et al. BMC Med Genomics. 2015 May;8:19; Eerola H et al. Breast Cancer Res. 2005 Nov;7:R93-100). Of note, this alteration is also referred to as 1731C>T in the published literature. 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.
Color Diagnostics, LLC DBA Color Health RCV000569665 SCV000682973 pathogenic Hereditary cancer-predisposing syndrome 2021-10-19 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in multiple individuals and families affected with breast and ovarian cancer (PMID: 15642173, 16455195, 25948282, 27425403, 28477318, 29310832, 29335924, 30606148). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
GeneKor MSA RCV000585637 SCV000693510 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing This variant is a single amino acid change from Glutamine to a Termination codon at amino acid residue 538 of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Truncating variants in the BRCA1 gene are known to be pathogenic. The mutation database ClinVar contains entries for this variant (Variation ID: 54309).
Mendelics RCV000496261 SCV000839282 pathogenic Hereditary breast ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000585637 SCV001469368 pathogenic not provided 2019-09-05 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 patient with expected phenotype for this gene, and not found in general population data.
Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar RCV000077492 SCV001519668 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 criteria provided, single submitter clinical testing
Invitae RCV000496261 SCV001590633 pathogenic Hereditary breast ovarian cancer syndrome 2023-02-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln538*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 15642173, 16455195, 25948282, 27425403, 28477318, 28724667, 29335924). This variant is also known as 1731C>T. ClinVar contains an entry for this variant (Variation ID: 54309). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077492 SCV000109290 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2008-04-25 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077492 SCV000144143 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2004-11-25 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496261 SCV000587151 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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