Submissions for variant NM_007294.4(BRCA1):c.1102G>T (p.Glu368Ter)

dbSNP: rs80357139

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)	RCV000111548	SCV000282254	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-22	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	RCV000111548	SCV000324954	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000448702	SCV000537639	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.
Ambry Genetics	RCV000448702	SCV002742899	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-04	criteria provided, single submitter	clinical testing	The p.E368* pathogenic mutation (also known as c.1102G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 1102. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation has been reported in multiple individuals with hereditary breast and ovarian cancer (HBOC) syndrome (Maleva I et al. Balkan J Med Genet, 2012 Dec;15:81-5; Azzollini J et al. Eur J Intern Med, 2016 Jul;32:65-71; Walker LC et al. Eur J Hum Genet, 2017 04;25:432-438; Jakimovska M et al. Breast Cancer Res Treat, 2018 Apr;168:745-753; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). 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.
Invitae	RCV000496434	SCV003443191	pathogenic	Hereditary breast ovarian cancer syndrome	2022-01-24	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: 54128). This premature translational stop signal has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 27062684, 29335924, 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu368*) 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)	RCV000111548	SCV000144009	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496434	SCV000587106	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research