Submissions for variant NM_007294.4(BRCA1):c.1978del (p.Val660fs)

dbSNP: rs886039988

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257100	SCV000323384	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	RCV000257100	SCV000325207	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003237806	SCV002009463	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496498	SCV002145327	pathogenic	Hereditary breast ovarian cancer syndrome	2023-02-10	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val660Serfs*41) 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). ClinVar contains an entry for this variant (Variation ID: 266208). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV003298331	SCV004004336	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-01	criteria provided, single submitter	clinical testing	The c.1978delG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1978, causing a translational frameshift with a predicted alternate stop codon (p.V660Sfs*41). This alteration has been reported in an individual with a personal history of breast and ovarian cancers (Cui J et al. Front Oncol, 2016 Apr;6:92). 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.
Baylor Genetics	RCV000257100	SCV004215032	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-08-08	criteria provided, single submitter	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496498	SCV000587178	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research