Submissions for variant NM_007294.4(BRCA1):c.4956G>A (p.Met1652Ile)

gnomAD frequency: 0.01348  dbSNP: rs1799967

Total submissions: 46

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112434	SCV000244374	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 = 0.0000148. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.02243 (European), derived from 1000 genomes (2012-04-30).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048709	SCV000076722	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000112434	SCV000153999	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-02	criteria provided, single submitter	literature only
GeneDx	RCV000120261	SCV000167315	benign	not specified	2013-09-04	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.
Ambry Genetics	RCV000128916	SCV000172783	benign	Hereditary cancer-predisposing syndrome	2014-11-18	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	RCV000112434	SCV000195935	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-04-21	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000120261	SCV000226314	benign	not specified	2014-08-07	criteria provided, single submitter	clinical testing
Vantari Genetics	RCV000128916	SCV000267003	uncertain significance	Hereditary cancer-predisposing syndrome	2015-12-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128916	SCV000292109	benign	Hereditary cancer-predisposing syndrome	2014-11-19	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000048709	SCV000297227	benign	Hereditary breast ovarian cancer syndrome	2015-11-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000120261	SCV000311798	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000112434	SCV000403056	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2018-01-24	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000048709	SCV000494358	benign	Hereditary breast ovarian cancer syndrome	2014-01-27	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000476093	SCV000540962	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000112434	SCV000575712	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-09-03	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000120261	SCV000586904	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034756	SCV000602685	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000120261	SCV000693618	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112434	SCV000743385	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	RCV000112434	SCV000744605	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-09-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000112434	SCV001140499	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000112434	SCV001440666	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-01-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000120261	SCV001470003	benign	not specified	2020-06-15	criteria provided, single submitter	clinical testing
Molecular Endocrinology Laboratory, Christian Medical College	RCV000112434	SCV002003992	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1		criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034756	SCV002009432	benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000048709	SCV002025923	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034756	SCV002498277	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	BRCA1: PM5, BP4, BS1, BS2
Genetics Program, Instituto Nacional de Cancer	RCV000048709	SCV002515221	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000128916	SCV002537797	benign	Hereditary cancer-predisposing syndrome	2020-01-02	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120261	SCV002550961	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112434	SCV004016750	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	RCV000112434	SCV004817610	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000034756	SCV005251028	benign	not provided		criteria provided, single submitter	not provided
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034756	SCV000043153	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
ITMI	RCV000120261	SCV000084413	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112434	SCV000145222	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000112434	SCV000189346	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2011-03-08	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000112434	SCV000733603	benign	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000034756	SCV000778735	benign	not provided	2016-11-17	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000128916	SCV000787908	benign	Hereditary cancer-predisposing syndrome	2017-11-15	no assertion criteria provided	clinical testing
Brotman Baty Institute, University of Washington	RCV000112434	SCV001243268	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Center of Medical Genetics and Primary Health Care	RCV001270155	SCV001450446	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000120261	SCV001551789	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000120261	SCV001798105	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000120261	SCV001906051	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000120261	SCV001952918	benign	not specified		no assertion criteria provided	clinical testing