Submissions for variant NM_007294.4(BRCA1):c.1255del (p.Glu418_Val419insTer)

dbSNP: rs80357535

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)	RCV000111574	SCV000299565	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Genetic Services Laboratory, University of Chicago	RCV000111574	SCV000246803	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2014-11-06	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000111574	SCV000324997	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001010575	SCV001170798	pathogenic	Hereditary cancer-predisposing syndrome	2023-12-27	criteria provided, single submitter	clinical testing	The c.1255delG pathogenic mutation (also known as p.V419*), located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1255. This changes the amino acid from a valine to a stop codon within coding exon 9. This mutation has been previously described in 1/238 women considered to be at high risk for hereditary breast and ovarian cancer based on their personal and/or family history (Frank TS et al. J. Clin. Oncol. 1998 Jul;16:2417-25). 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	RCV000496803	SCV001586051	pathogenic	Hereditary breast ovarian cancer syndrome	2017-10-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val419*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 9667259). This variant is also known as c.1374delG in the literature. ClinVar contains an entry for this variant (Variation ID: 54177). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111574	SCV000144041	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1997-11-14	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496803	SCV000587116	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research