Submissions for variant NM_007294.4(BRCA1):c.4903G>T (p.Glu1635Ter)

dbSNP: rs200432771

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)	RCV000112420	SCV000300171	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	RCV000129569	SCV000184351	pathogenic	Hereditary cancer-predisposing syndrome	2019-02-06	criteria provided, single submitter	clinical testing	The p.E1635* pathogenic mutation (also known as c.4903G>T), located in coding exon 14 of the BRCA1 gene, results from a G to T substitution at nucleotide position 4903. This changes the amino acid from a glutamic acid to a stop codon within coding exon 14. This mutation was previously identified in a breast and ovarian cancer family of Southern Chinese ancestry (Kwong A et al. PLoS ONE 2012; 7:e43994). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). 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	RCV000112420	SCV000326061	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496337	SCV001582578	pathogenic	Hereditary breast ovarian cancer syndrome	2023-11-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1635*) 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 and/or ovarian cancer (PMID: 22970155). ClinVar contains an entry for this variant (Variation ID: 55311). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112420	SCV000145206	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2013-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496337	SCV000587432	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Brotman Baty Institute, University of Washington	RCV000112420	SCV001243815	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro