Submissions for variant NM_007294.4(BRCA1):c.1971A>G (p.Gln657=)

gnomAD frequency: 0.00707  dbSNP: rs28897679

Total submissions: 29

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111743	SCV000244747	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-01-12	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.01829 (African), derived from 1000 genomes (2012-04-30).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000047668	SCV000075681	benign	Hereditary breast ovarian cancer syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Counsyl	RCV000111743	SCV000153992	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-02	criteria provided, single submitter	literature only
GeneDx	RCV000173846	SCV000167246	benign	not specified	2013-09-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000111743	SCV000195898	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162491	SCV000212871	benign	Hereditary cancer-predisposing syndrome	2015-11-06	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000173846	SCV000225007	benign	not specified	2015-09-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000111743	SCV000403069	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000047668	SCV000494305	benign	Hereditary breast ovarian cancer syndrome	2014-03-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000466198	SCV000540972	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000111743	SCV000575716	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-08-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656638	SCV000602680	benign	not provided	2024-05-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162491	SCV000683005	benign	Hereditary cancer-predisposing syndrome	2015-04-21	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000111743	SCV000743422	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000111743	SCV000744669	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000173846	SCV000806906	benign	not specified	2017-01-30	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769721	SCV000901142	benign	Breast and/or ovarian cancer	2016-03-08	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000047668	SCV002025996	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000173846	SCV002070455	benign	not specified	2021-05-24	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000047668	SCV002515185	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000173846	SCV002551026	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000111743	SCV004016794	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000656638	SCV005251072	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111743	SCV000144265	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1998-11-17	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353799	SCV000591359	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	Borg_2010 Fackenthal_2012
Mayo Clinic Laboratories, Mayo Clinic	RCV000656638	SCV000778765	likely benign	not provided	2017-03-09	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000162491	SCV000787894	likely benign	Hereditary cancer-predisposing syndrome	2017-09-29	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000173846	SCV001905714	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000173846	SCV001956274	benign	not specified		no assertion criteria provided	clinical testing