Submissions for variant NM_007294.4(BRCA1):c.4039A>G (p.Arg1347Gly)

gnomAD frequency: 0.00419  dbSNP: rs28897689

Total submissions: 48

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112230	SCV000244351	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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048417	SCV000076430	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000112230	SCV000153993	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-02	criteria provided, single submitter	literature only
GeneDx	RCV000120280	SCV000167299	benign	not specified	2014-10-10	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	RCV000112230	SCV000195925	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-11-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000120280	SCV000202265	benign	not specified	2014-05-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162493	SCV000212875	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.
Vantari Genetics	RCV000162493	SCV000267004	benign	Hereditary cancer-predisposing syndrome	2016-01-18	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000048417	SCV000267853	likely benign	Hereditary breast ovarian cancer syndrome	2016-04-25	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034747	SCV000280661	likely benign	not provided	2016-04-18	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000048417	SCV000494321	benign	Hereditary breast ovarian cancer syndrome	2014-02-24	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000120280	SCV000538435	likely benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.6% (430/66720) European chromosomes, 2 homozygotes; ClinVar: 8 labs classify as B/LB
Baylor Genetics	RCV000462353	SCV000540986	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000120280	SCV000586896	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Department of Pathology and Molecular Medicine, Queen's University	RCV000120280	SCV000588052	benign	not specified	2017-04-20	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120280	SCV000593660	benign	not specified	2019-02-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034747	SCV000602688	benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112230	SCV000743398	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	RCV000112230	SCV000744621	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000120280	SCV000806942	benign	not specified	2017-02-20	criteria provided, single submitter	clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000120280	SCV000864299	likely benign	not specified	2017-06-12	criteria provided, single submitter	clinical testing	BS1,BP1,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is a missense alteration in a gene for which primarily truncating variants are known to cause disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Color Diagnostics, LLC DBA Color Health	RCV000162493	SCV000902551	benign	Hereditary cancer-predisposing syndrome	2015-10-13	criteria provided, single submitter	clinical testing
Mendelics	RCV000112230	SCV001140539	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034747	SCV001151328	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	BRCA1: BP4, BS2
Illumina Laboratory Services, Illumina	RCV000112230	SCV001283852	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2017-04-27	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170593	SCV001333181	benign	Breast and/or ovarian cancer	2023-05-26	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000112230	SCV001429072	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2018-07-09	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000048417	SCV002025947	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000048417	SCV002515206	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000162493	SCV002538255	benign	Hereditary cancer-predisposing syndrome	2020-10-01	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120280	SCV002550983	benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112230	SCV004016771	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	RCV000112230	SCV004817719	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000034747	SCV005251054	benign	not provided		criteria provided, single submitter	not provided
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034747	SCV000043161	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
ITMI	RCV000120280	SCV000084432	not provided	not specified	2013-09-19	no assertion provided	reference population
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112230	SCV000144942	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1999-12-30	no assertion criteria provided	clinical testing
Pathway Genomics	RCV000112230	SCV000187723	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-07-24	no assertion criteria provided	literature only
Sharing Clinical Reports Project (SCRP)	RCV000112230	SCV000189341	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2011-03-09	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000120280	SCV000587368	benign	not specified	2014-01-31	no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000120280	SCV000591481	benign	not specified		no assertion criteria provided	clinical testing	The p.Arg1347Gly variant is not expected to have clinical significance because it has been reported 44 times (in heterozygozous or homozygous form) with co-occurrence in individuals with known deleterious mutation in the BRCA1 gene (Tavtigian_2006_16014699). This variant is also reported in dbSNP (rs28897689) with an average heterozygosity of 0.010+/-0.068. Pathogenic variants have been reported as co-occuring with this variant: BRCA1 (1) c.5077_5080delinsTTCATTCTGC (p.Asp1692_Ala1693insPheIle) (2) c.2617dup (p.Ser873PhefsX30) (3) c.IVS5+3A>G (c.212+3A>G) AND BRCA2 (c.1420delC (p.Glu475AsnfsX10)), increasing the likelihood the p.Arg1347 variant does not have clinical significance. Based on the above information this variant is considered benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000112230	SCV000733616	benign	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000034747	SCV000778742	likely benign	not provided	2017-03-31	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000162493	SCV000787903	likely benign	Hereditary cancer-predisposing syndrome	2017-07-17	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000120280	SCV001800181	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000120280	SCV001906230	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000120280	SCV001956103	benign	not specified		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000112230	SCV004244013	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2020-03-02	no assertion criteria provided	clinical testing