ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.668del (p.Lys223fs)

dbSNP: rs80357537
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000049085 SCV000077098 uncertain significance Hereditary breast ovarian cancer syndrome 2023-08-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys223Argfs*11) in the BRCA1 gene. Loss-of-function variants in BRCA1 are expected to be pathogenic (PMID: 20104584). However, an in-frame BRCA1 isoform lacking exons 8 and 9 (also known as exons 9 and 10) is highly expressed in blood from unaffected individuals and in normal breast tissue; this isoform may retain protein function and could functionally rescue loss-of-function variants within exons 8-9 (PMID: 24569164). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 55659). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112758 SCV000326374 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000112758 SCV004216920 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2022-08-26 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112758 SCV000145649 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 1999-04-06 no assertion criteria provided clinical testing

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