Submissions for variant NM_007294.4(BRCA1):c.783T>G (p.Tyr261Ter)

dbSNP: rs80357321

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031278	SCV000299482	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.
GeneDx	RCV000212162	SCV000210087	pathogenic	not provided	2021-06-30	criteria provided, single submitter	clinical testing	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 (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 902T>G; Observed in individuals with personal or family history of BRCA1-related cancer (van der Hout 2006); This variant is associated with the following publications: (PMID: 25525159, 25823446, 27535533, 29446198, 16683254)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031278	SCV000326407	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000509946	SCV000607773	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-23	criteria provided, single submitter	clinical testing	The p.Y261* pathogenic mutation (also known as c.783T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 783. This changes the amino acid from a tyrosine to a stop codon within coding exon 9. This mutation has been identified in a Dutch family with Hereditary Breast and Ovarian Cancer (HBOC) Syndrome (van der Hout AH at al. Hum. Mutat. 2006 Jul;27(7):654-66). 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 variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212162	SCV000887734	pathogenic	not provided	2018-04-05	criteria provided, single submitter	clinical testing
Invitae	RCV000496530	SCV001580446	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr261*) 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: 16683254). ClinVar contains an entry for this variant (Variation ID: 37697). For these reasons, this variant has been classified as Pathogenic.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000212162	SCV002009406	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000031278	SCV004216877	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-11-28	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031278	SCV000053883	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2011-05-16	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031278	SCV000145681	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2013-05-21	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496530	SCV000587075	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research