Submissions for variant NM_007294.4(BRCA1):c.4678G>T (p.Gly1560Ter)

dbSNP: rs80357349

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077583	SCV000300152	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	RCV000131834	SCV000186889	pathogenic	Hereditary cancer-predisposing syndrome	2018-01-02	criteria provided, single submitter	clinical testing	The p.G1560* pathogenic mutation (also known as c.4678G>T), located in coding exon 14 of the BRCA1 gene, results from a G to T substitution at nucleotide position 4678. This changes the amino acid from a glycine to a stop codon within coding exon 14. This mutation (designated as 4797G>T) was previously identified in a cohort of 131 women diagnosed with non-mucinous epithelial ovarian cancer (Schrader KA et al. Obstet. Gynecol. 2012 Aug;120:235-40). 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	RCV000077583	SCV000326029	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000508627	SCV000605889	pathogenic	not provided	2017-03-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131834	SCV000909014	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-01	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 15 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 been reported in an individual affected with ovarian cancer (PMID: 22776961). 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	RCV000496210	SCV003516070	pathogenic	Hereditary breast ovarian cancer syndrome	2022-06-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly1560*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55257). This variant is also known as 4797G>T. This premature translational stop signal has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer (HBOC) syndrome (PMID: 22776961, 29446198). This variant is not present in population databases (gnomAD no frequency).
Sharing Clinical Reports Project (SCRP)	RCV000077583	SCV000109386	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2011-11-08	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077583	SCV000145157	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	RCV000496210	SCV000587420	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research