Submissions for variant NM_007294.4(BRCA1):c.2761C>T (p.Gln921Ter)

dbSNP: rs80357377

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111933	SCV000299829	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	RCV000221485	SCV000277204	pathogenic	Hereditary cancer-predisposing syndrome	2018-11-30	criteria provided, single submitter	clinical testing	The p.Q921* pathogenic mutation (also known as c.2761C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 2761. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration was identified in a patient with ovarian cancer (Cunningham JM et al. Sci Rep, 2014 Feb;4:4026). 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	RCV000111933	SCV000325457	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000111933	SCV000821709	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal at codon 921 of the BRCA1 protein. It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular variant has been described in the mutation database ClinVar (Variation ID: 54673).
Color Diagnostics, LLC DBA Color Health	RCV000221485	SCV000904993	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.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana	RCV000111933	SCV001499617	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-04-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496230	SCV001582244	pathogenic	Hereditary breast ovarian cancer syndrome	2023-09-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln921*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54673). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 20104584).
GeneDx	RCV003148644	SCV003837390	pathogenic	not provided	2023-02-28	criteria provided, single submitter	clinical testing	Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Reported in association with hereditary breast and/or ovarian cancer (Phelan et al., 2002; Cunningham et al., 2014; Rebbeck et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2880C>T; This variant is associated with the following publications: (PMID: 25525159, 29446198, 11896095, 31159747, 32377563, 21702907, 24504028, 20858050, 12402332, 31853058, 34290354, 20104584, 35165121)
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111933	SCV000144537	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	RCV000496230	SCV000587254	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research