Submissions for variant NM_007294.4(BRCA1):c.1612C>T (p.Gln538Ter)

dbSNP: rs80356893

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077492	SCV000299626	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	RCV000077492	SCV000325108	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000507406	SCV000602689	pathogenic	not specified	2016-10-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000569665	SCV000665136	pathogenic	Hereditary cancer-predisposing syndrome	2017-06-01	criteria provided, single submitter	clinical testing	The p.Q538* pathogenic mutation (also known as c.1612C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 1612. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This mutation has been reported in numerous individuals with early onset breast cancer and/or familial breast and ovarian cancer (Ahn SH et al. Cancer Lett. 2007 Jan;245:90-5; Kluska A et al. BMC Med Genomics. 2015 May;8:19; Eerola H et al. Breast Cancer Res. 2005 Nov;7:R93-100). Of note, this alteration is also referred to as 1731C>T in the published literature. 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.
Color Diagnostics, LLC DBA Color Health	RCV000569665	SCV000682973	pathogenic	Hereditary cancer-predisposing syndrome	2021-10-19	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 been observed in multiple individuals and families affected with breast and ovarian cancer (PMID: 15642173, 16455195, 25948282, 27425403, 28477318, 29310832, 29335924, 30606148). 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.
GeneKor MSA	RCV000585637	SCV000693510	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This variant is a single amino acid change from Glutamine to a Termination codon at amino acid residue 538 of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Truncating variants in the BRCA1 gene are known to be pathogenic. The mutation database ClinVar contains entries for this variant (Variation ID: 54309).
Mendelics	RCV000496261	SCV000839282	pathogenic	Hereditary breast ovarian cancer syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000585637	SCV001469368	pathogenic	not provided	2019-09-05	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar	RCV000077492	SCV001519668	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496261	SCV001590633	pathogenic	Hereditary breast ovarian cancer syndrome	2023-02-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln538*) 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: 15642173, 16455195, 25948282, 27425403, 28477318, 28724667, 29335924). This variant is also known as 1731C>T. ClinVar contains an entry for this variant (Variation ID: 54309). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000077492	SCV000109290	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2008-04-25	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077492	SCV000144143	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2004-11-25	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496261	SCV000587151	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research