Submissions for variant NM_007294.4(BRCA1):c.4321dup (p.Asp1441fs)

dbSNP: rs80357748

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)	RCV000112315	SCV000300102	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112315	SCV000325920	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001022292	SCV001184008	pathogenic	Hereditary cancer-predisposing syndrome	2019-05-16	criteria provided, single submitter	clinical testing	The c.4321dupG pathogenic mutation, located in coding exon 11 of the BRCA1 gene, results from a duplication of G at nucleotide position 4321, causing a translational frameshift with a predicted alternate stop codon (p.D1441Gfs*21). This mutation has been reported in an individual with ovarian cancer who also had a family history of breast and/or ovarian cancer (Pal T et al. Cancer 2005 Dec;104(12):2807-16). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284548	SCV001470390	pathogenic	not provided	2019-12-27	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496584	SCV003441898	pathogenic	Hereditary breast ovarian cancer syndrome	2022-03-26	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 55168). For these reasons, this variant has been classified as Pathogenic. This variant is also known as 4440insG. This premature translational stop signal has been observed in individual(s) with breast or ovarian cancer (PMID: 16284991, 30154229). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp1441Glyfs*21) 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).
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112315	SCV000145054	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496584	SCV000587390	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research