ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4945_4947delinsTTTT (p.Arg1649fs)

dbSNP: rs397509207
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Total submissions: 7
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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) RCV000257810 SCV000323809 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 RCV000257810 SCV000326069 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000637699 SCV000759170 pathogenic Hereditary breast ovarian cancer syndrome 2021-09-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023305 SCV001185162 pathogenic Hereditary cancer-predisposing syndrome 2021-01-21 criteria provided, single submitter clinical testing The c.4945_4947delAGAinsTTTT pathogenic mutation, located in coding exon 14 of the BRCA1 gene, results from the deletion of 3 nucleotides and insertion of 4 nucleotides at positions c.4945 to c.4947, causing a translational frameshift with a predicted alternate stop codon (p.R1649Ffs*30). This mutation has been detected in multiple breast or ovarian cancer patients (Bonadona V et al. Genes Chromosomes Cancer. 2005 Aug;43:404-13; Caux-Moncoutier V et al. Hum. Mutat. 2011 Mar;32:325-34; Donenberg T et al. Breast Cancer Res. Treat. 2016 Aug;159:131-8; Donenberg T et al. Breast Cancer Res Treat 2019 Apr;174(2):469-477). Of note, this mutation is also designated as 5064delAGA/insT4-ter1678 in published literature. 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.
Baylor Genetics RCV000257810 SCV004216916 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2022-09-02 criteria provided, single submitter clinical testing
GeneDx RCV004719684 SCV005325287 pathogenic not provided 2024-03-14 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; Also known as 5064_5066delinsTTTT; This variant is associated with the following publications: (PMID: 15887246, 33646313)
Fulgent Genetics, Fulgent Genetics RCV005016341 SCV005647125 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2024-06-17 criteria provided, single submitter clinical testing

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