Submissions for variant NM_007294.4(BRCA1):c.4161_4162del (p.Gln1388fs)

dbSNP: rs80357565

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112271	SCV000300082	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048461	SCV000076474	pathogenic	Hereditary breast ovarian cancer syndrome	2024-05-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1388Glufs*2) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast or ovarian cancer (PMID: 9667259, 11938448, 16234499, 18489799, 22460208, 23479189). This variant is also known as 4280delTC. ClinVar contains an entry for this variant (Variation ID: 55115). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000162873	SCV000213360	pathogenic	Hereditary cancer-predisposing syndrome	2021-01-11	criteria provided, single submitter	clinical testing	The c.4161_4162delTC pathogenic mutation, located in coding exon 10 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 4161 to 4162, causing a translational frameshift with a predicted alternate stop codon (p.Q1388Efs*2). This mutation has been reported in multiple families with breast and/or ovarian cancer (Nedelcu R et al. Eur. J. Hum. Genet. 2002 Feb;10:150-2; de Juan Jiménez I et al. Fam. Cancer 2013 Dec;12:767-77; Frank TS et al. J. Clin. Oncol. 1998 Jul;16:2417-25; Nanda R et al. JAMA 2005 Oct;294:1925-33). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112271	SCV000325869	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758824	SCV000887689	pathogenic	not provided	2018-08-09	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000112271	SCV004211758	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-05-25	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112271	SCV000144998	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2006-07-19	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000048461	SCV000587377	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Center for Precision Medicine, Meizhou People's Hospital	RCV002250542	SCV002520860	pathogenic	Familial cancer of breast		no assertion criteria provided	literature only