Submissions for variant NM_007294.4(BRCA1):c.3112G>T (p.Glu1038Ter)

dbSNP: rs80357161

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031090	SCV000299885	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	RCV000131907	SCV000186962	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-13	criteria provided, single submitter	clinical testing	The p.E1038* pathogenic mutation (also known as c.3112G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3112. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation has been reported as a germline mutation in a patient who developed a therapy related myeloid neoplasm 5 years after chemotherapy for ovarian cancer at the age of 56 (Schulz E et al. J. Med. Genet., 2012 Jul;49:422-8). 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	RCV000031090	SCV000325558	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000496578	SCV001579548	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1038*) 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 (PMID: 22652532, 29446198). ClinVar contains an entry for this variant (Variation ID: 37509). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000031090	SCV000053686	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2010-02-03	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031090	SCV000144641	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496578	SCV000587281	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research