Submissions for variant NM_007294.4(BRCA1):c.1292dup (p.Leu431fs)

dbSNP: rs80357528

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111584	SCV000299572	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	RCV000111584	SCV000325005	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000111584	SCV000564333	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001010799	SCV001171046	pathogenic	Hereditary cancer-predisposing syndrome	2018-01-14	criteria provided, single submitter	clinical testing	The c.1292dupT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of T at nucleotide position 1292, causing a translational frameshift with a predicted alternate stop codon (p.L431Ffs*5). This mutation has been reported in numerous individuals with hereditary breast and/or ovarian cancer, and has been reported as a common mutation in the Dutch population (Hogervorst FB et al. Nat. Genet., 1995 Jun;10:208-12; Janaviius R. EPMA J, 2010 Sep;1:397-412; Vos JR et al. Cancer Epidemiol. Biomarkers Prev., 2014 Nov;23:2482-91; Karami F et al. Biomed Res Int, 2013 Nov;2013:928562; Papelard H et al. Br. J. Cancer, 2000 Sep;83:719-24). Of note, this alteration is also designated as 1411insT and 1409insT in published literature. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496836	SCV001587051	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54188). This variant is also known as 1409insT and 1411insT. This premature translational stop signal has been observed in individual(s) with breast cancer and pancreatic cancer (PMID: 7663517, 28900739, 29339979). This variant is present in population databases (rs80357528, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Leu431Phefs*5) 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)	RCV000111584	SCV000144052	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	RCV000496836	SCV000587119	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001682749	SCV001905827	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001682749	SCV001932009	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001682749	SCV001968678	pathogenic	not provided		no assertion criteria provided	clinical testing