ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.923del (p.Ser308fs) (rs80357953)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567610 SCV000673056 pathogenic Hereditary cancer-predisposing syndrome 2017-03-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000111511 SCV000143953 pathogenic Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Color RCV000567610 SCV000904136 pathogenic Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111511 SCV000326460 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111511 SCV000299505 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000236025 SCV000293265 pathogenic not provided 2017-10-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.923delG at the cDNA level and p.Ser308ThrfsX6 (S308TfsX6) at the protein level. The normal sequence, with the base that is deleted in brackets, is TAAAA[G]CAAA. The deletion causes a frameshift, which changes a Serine to a Threonine at codon 308, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.923delG, also published as BRCA1 1042delG using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer (Judkins 2005) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000779891 SCV000916781 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-17 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.923delG (p.Ser308ThrfsX6) 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 allele was found at a frequency of 4.1e-06 in 246104 control chromosomes. c.923delG has been reported in the literature and reputable databases in individuals affected with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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