Submissions for variant NM_007294.4(BRCA1):c.3544C>T (p.Gln1182Ter)

dbSNP: rs80357296

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112114	SCV000299962	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112114	SCV000325679	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000112114	SCV000564351	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001020568	SCV001182064	pathogenic	Hereditary cancer-predisposing syndrome	2019-12-11	criteria provided, single submitter	clinical testing	The p.Q1182* pathogenic mutation (also known as c.3544C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3544. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration has been reported in multiple large studies of BRCA1/2 mutation positive families, including individuals from Norway, Brazil, Japan, Turkey, and Bulgaria (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Palmero EI et al. Sci Rep, 2018 06;8:9188;Momozawa Y et al. Nat Commun, 2018 10;9:4083; Laitman Y et al. Hum. Mutat., 2019 11;40:e1-e23). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496733	SCV001583037	pathogenic	Hereditary breast ovarian cancer syndrome	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1182*) 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 clinical features of hereditary breast and ovarian cancer syndrome (PMID: 29339979, 29446198, 29907814, 30287823). ClinVar contains an entry for this variant (Variation ID: 54913). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000112114	SCV005058212	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2024-03-29	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112114	SCV000144786	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2003-12-23	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000112114	SCV000189338	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-04-10	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496733	SCV000587319	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000112114	SCV002589107	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-26	no assertion criteria provided	clinical testing
Laboratory for Genotyping Development, RIKEN	RCV003162409	SCV002758205	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112114	SCV003927176	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-05	no assertion criteria provided	clinical testing	A known pathogenic mutation in the BRCA1 gene was detected in this specimen. This mutation (c.3544C>T) in exon 10 of BRCA1 gene results in a stop codon which causes a truncated non-functional protein. This mutation has 7 entries in ClinVar all of which are listed as pathogenic and not listed in ExAC database.