ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4088C>G (p.Ser1363Ter)

dbSNP: rs398122680
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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) RCV000241411 SCV000300069 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 RCV000241411 SCV000325842 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000483270 SCV000568408 pathogenic not provided 2018-08-07 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4088C>G at the cDNA level and p.Ser1363Ter (S1363X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least two patients undergoing genetic testing for hereditary breast and/or ovarian cancer (Caux-Moncoutier 2009, Michils 2012) and is considered pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483270 SCV000887685 pathogenic not provided 2018-04-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001021838 SCV001183505 pathogenic Hereditary cancer-predisposing syndrome 2017-12-08 criteria provided, single submitter clinical testing The p.S1363* pathogenic mutation (also known as c.4088C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 4088. This changes the amino acid from a serine to a stop codon within coding exon 9. 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.
Invitae RCV001048872 SCV001212898 pathogenic Hereditary breast ovarian cancer syndrome 2023-02-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1363*) 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 present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 254452). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000483270 SCV004224861 pathogenic not provided 2022-10-20 criteria provided, single submitter clinical testing PP5, PM2, PVS1
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000483270 SCV004242815 pathogenic not provided 2024-02-06 criteria provided, single submitter clinical testing

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