Submissions for variant NM_007294.4(BRCA1):c.4401del (p.Asn1468fs)

dbSNP: rs587781611

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000238940	SCV000300118	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.
Ambry Genetics	RCV000129698	SCV000184499	pathogenic	Hereditary cancer-predisposing syndrome	2020-11-16	criteria provided, single submitter	clinical testing	The c.4401delG pathogenic mutation, located in coding exon 12 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 4401, causing a translational frameshift with a predicted alternate stop codon (p.N1468Ifs*37). 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	RCV000238940	SCV000296395	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-07	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000238940	SCV000325951	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000496731	SCV002235733	pathogenic	Hereditary breast ovarian cancer syndrome	2020-12-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 141260). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn1468Ilefs*37) 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).
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496731	SCV000587396	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research