Submissions for variant NM_007294.4(BRCA1):c.3319G>T (p.Glu1107Ter)

dbSNP: rs80357106

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112058	SCV000299914	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	RCV000112058	SCV000325609	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000112058	SCV000564318	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000570252	SCV000668382	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-14	criteria provided, single submitter	clinical testing	The p.E1107* pathogenic mutation (also known as c.3319G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3319. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation has been identified in Danish cohorts of breast and ovarian cancer patients and is recognized as a founder mutation in this population (Soegaard M et al. Clin. Cancer Res. 2008 Jun;14:3761-7; Thomassen M et al. Acta Oncol 2008;47:772-7; Janaviius R. EPMA J 2010 Sep;1:397-412). One study focusing on female cancer risks found that this mutation may be associated with higher risk for ovarian cancer when compared to other BRCA1 mutations in the Danish population (Nielsen HR et al. Fam. Cancer 2016 Oct;15:507-12). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated as 3438G>T 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.
Color Diagnostics, LLC DBA Color Health	RCV000570252	SCV001348545	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496209	SCV002120409	pathogenic	Hereditary breast ovarian cancer syndrome	2025-01-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1107*) 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 clinical features of hereditary breast and ovarian cancer (HBOC) syndrome (PMID: 18559594, 29446198). This variant is also known as c.3438G>T. ClinVar contains an entry for this variant (Variation ID: 54836). For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002267822	SCV002551002	pathogenic	not provided	2025-03-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000112058	SCV004215141	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-05	criteria provided, single submitter	clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000112058	SCV005045957	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2024-05-27	criteria provided, single submitter	clinical testing	PVS1; PM2_supporting; PM5_PTC_Strong
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112058	SCV000144711	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496209	SCV000587297	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000112058	SCV004244055	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-03-02	no assertion criteria provided	clinical testing