Submissions for variant NM_007294.4(BRCA1):c.5492del (p.Pro1831fs)

dbSNP: rs80357582

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112680	SCV000300269	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.
GeneKor MSA	RCV000238684	SCV000296783	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change deletes one nucleotide base causing a frameshift and the creation of a premature translation stop signal 3 amino acid residues later. This is expected to result in an absent or disrupted protein product.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112680	SCV000326337	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000238684	SCV001447818	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345356	SCV002652707	pathogenic	Hereditary cancer-predisposing syndrome	2016-12-21	criteria provided, single submitter	clinical testing	The c.5492delC pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 5492, causing a translational frameshift with a predicted alternate stop codon (p.P1831Lfs*3). This frameshift occurs at the 3' terminus of BRCA1, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 33 amino acids of the protein. This alteration results in loss of very crucial amino acids from codons 1831 to 1855, which are part of the second BRCT functional domain. In addition, this mutation has been reported in numerous high-risk individuals with breast and/or ovarian cancer (Arnold N et al. Hum. Mutat., 1999;14:333-9; Konstantopoulou I et al. Clin. Genet., 2014 Jan;85:36-42; Meindl A et al. Int. J. Cancer, 2002 Feb;97:472-80). Of note, this mutation is also designated as 5611delC in published literature. This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Baylor Genetics	RCV000112680	SCV004215126	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-22	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112680	SCV000145546	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	RCV000496304	SCV000587512	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research