ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3672del (p.Cys1225fs) (rs398122677)

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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) RCV000077129 SCV000299991 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000130025 SCV000184851 pathogenic Hereditary cancer-predisposing syndrome 2019-04-08 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000168007 SCV000218658 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys1225Alafs*10) 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 not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 91612). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077129 SCV000325720 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000485024 SCV000570870 pathogenic not provided 2016-06-30 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.3672delC at the cDNA level and p.Cys1225AlafsX10 (C1225AfsX10) at the protein level. The normal sequence, with the base that is deleted in braces, is TTCC[C]TGCT. The deletion causes a frameshift which changes a Cysteine to an Alanine at codon 1225, and creates a premature stop codon at position 10 of the new reading frame. Using alternate nomenclature, this variant would be defined as BRCA1 3791delC. 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. We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000485024 SCV000600342 pathogenic not provided 2016-10-27 criteria provided, single submitter clinical testing
Color RCV000130025 SCV000688448 pathogenic Hereditary cancer-predisposing syndrome 2017-04-04 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077129 SCV000108926 pathogenic Breast-ovarian cancer, familial 1 2012-12-27 no assertion criteria provided clinical testing

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