Submissions for variant NM_007294.4(BRCA1):c.924del (p.Ser308fs)

dbSNP: rs397509336

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257298	SCV000323931	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	RCV000257298	SCV000326461	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003162425	SCV003856611	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-06	criteria provided, single submitter	clinical testing	The c.924delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 924, causing a translational frameshift with a predicted alternate stop codon (p.S308Rfs*6). This alteration was identified in an individual with a family history of breast and/or ovarian cancer (Stoppa-Lyonnet D et al. Am J Hum Genet, 1997 May;60:1021-30). Of note, this alteration is also known as 1043delC in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496412	SCV004296850	pathogenic	Hereditary breast ovarian cancer syndrome	2024-04-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser308Argfs*6) 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 hereditary breast and ovarian cancer syndrome (PMID: 9150149). This variant is also known as c.1043delC (ter313). ClinVar contains an entry for this variant (Variation ID: 55755). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496412	SCV000587086	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research