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	2020-08-05	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.
Invitae	RCV000496803	SCV001586051	pathogenic	Hereditary breast ovarian cancer syndrome	2017-10-01	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). 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). This variant is not present in population databases (ExAC no frequency). 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.
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