ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1407_1408del (p.Ser470fs)

dbSNP: rs879255476
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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) RCV000238667 SCV000323316 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 RCV000238667 SCV000325063 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000496818 SCV000918671 pathogenic Hereditary breast ovarian cancer syndrome 2023-10-16 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1407_1408delAA (p.Ser470ProfsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251228 control chromosomes. c.1407_1408delAA has been reported in the literature in individuals affected with breast cancer (e.g. Chavarri-Guerra_2022). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35438911). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000496818 SCV001235838 pathogenic Hereditary breast ovarian cancer syndrome 2023-02-14 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 252863). This sequence change creates a premature translational stop signal (p.Ser470Profs*9) 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: 29446198). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002392750 SCV002698911 pathogenic Hereditary cancer-predisposing syndrome 2022-01-12 criteria provided, single submitter clinical testing The c.1407_1408delAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 1407 to 1408, causing a translational frameshift with a predicted alternate stop codon (p.S470Pfs*9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Fulgent Genetics, Fulgent Genetics RCV002479951 SCV002800163 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2022-04-10 criteria provided, single submitter clinical testing
GeneDx RCV003165676 SCV003915199 pathogenic not provided 2022-10-10 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1526_1527del
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003165676 SCV004222564 pathogenic not provided 2022-06-24 criteria provided, single submitter clinical testing This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in one or more individual(s) with triple negative breast cancer (PMID: 35438911 (2022)). Based on the available information, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000238667 SCV000297466 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2012-11-12 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496818 SCV000587133 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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