Submissions for variant NM_007294.4(BRCA1):c.3548A>G (p.Lys1183Arg)

gnomAD frequency: 0.30784  dbSNP: rs16942

Total submissions: 36

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112115	SCV000244342	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-08-10	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000204. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.3304 (Asian), 0.2154 (African), 0.3562 (European), derived from 1000 genomes (2012-04-30).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048229	SCV000076242	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000112115	SCV000154008	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-02	criteria provided, single submitter	literature only	High frequency in a 1kG or ESP population: 32.4 %.
Ambry Genetics	RCV000128991	SCV000172884	benign	Hereditary cancer-predisposing syndrome	2015-11-13	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.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000112115	SCV000195921	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-11-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000120278	SCV000202266	benign	not specified	2016-01-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128991	SCV000292080	benign	Hereditary cancer-predisposing syndrome	2014-11-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000120278	SCV000311795	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000112115	SCV000403059	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2018-03-06	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	RCV000048229	SCV000494319	benign	Hereditary breast ovarian cancer syndrome	2013-12-19	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000460753	SCV000540957	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000120278	SCV000586893	benign	not specified	2017-04-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034742	SCV000602662	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000120278	SCV000605733	benign	not specified	2016-12-19	criteria provided, single submitter	clinical testing	This variant is not expected to have clinical significance because it has been i dentified in 50% (8252/16506) of South Asian, including 2129 homozygotes, and 39 % (2602/66384) of European chromosomes, including 3592 homozygotes, by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNPrs16942). I n addition, this variant was classified as benign on August 10, 2015 by the Clin Gen- approved ENIGMA expert panel (ClinVar SCV000244342.1)
GeneKor MSA	RCV000120278	SCV000693612	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112115	SCV000743405	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000112115	SCV000744632	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-09-21	criteria provided, single submitter	clinical testing
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Faculty of Medicine Ramathibodi Hospital, Mahidol University	RCV000770891	SCV000899177	benign	Breast carcinoma	2019-04-22	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000460753	SCV001251942	benign	Familial cancer of breast	2020-05-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000048229	SCV002025955	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited	RCV000112115	SCV002097602	benign	Breast-ovarian cancer, familial, susceptibility to, 1		criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000048229	SCV002515199	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000128991	SCV002538216	benign	Hereditary cancer-predisposing syndrome	2019-12-11	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002490466	SCV002802805	benign	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S	2022-05-06	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112115	SCV004016741	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000112115	SCV004817790	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000034742	SCV005251058	benign	not provided		criteria provided, single submitter	not provided
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034742	SCV000043166	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
ITMI	RCV000120278	SCV000084430	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112115	SCV000144787	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2004-02-20	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000112115	SCV000189339	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2011-03-22	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000112115	SCV000733625	benign	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000034742	SCV000778745	benign	not provided	2015-10-02	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000120278	SCV001553628	benign	not specified		no assertion criteria provided	clinical testing	#N/A
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000120278	SCV001905718	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000120278	SCV001959074	benign	not specified		no assertion criteria provided	clinical testing