ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3388del (p.Ser1130fs)

dbSNP: rs886040123
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Total submissions: 5
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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) RCV000257795 SCV000323603 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-10-18 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 RCV000257795 SCV000325642 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000486723 SCV000564728 pathogenic not provided 2014-12-22 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.3388delT at the cDNA level and p.Ser1130GlnfsX4 (S1130QfsX4) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GATT[T]CAGA. The deletion causes a frameshift, which changes a Serine to a Glutamine at codon 1130, and creates a premature stop codon at position 4 of the new reading frame. Using alternate nomenclature, this variant would be defined as BRCA1 3507delT. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Ambry Genetics RCV003343736 SCV004058399 pathogenic Hereditary cancer-predisposing syndrome 2023-06-20 criteria provided, single submitter clinical testing The c.3388delT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 3388, causing a translational frameshift with a predicted alternate stop codon (p.S1130Qfs*4). This alteration has been identified in multiple breast and/or ovarian cancer families (Rebbeck TR et al. Hum Mutat, 2018 May;39:593-620; Momozawa Y et al. JAMA Oncol, 2022 Jun;8:871-878). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Laboratory for Genotyping Development, RIKEN RCV003165705 SCV002758470 pathogenic Gastric cancer 2021-07-01 no assertion criteria provided research

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