ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2521C>T (p.Arg841Trp) (rs1800709)

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Total submissions: 36
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000019251 SCV000244321 benign Breast-ovarian cancer, familial 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 = 0.00000000000229
Invitae RCV000047867 SCV000075880 benign Hereditary breast and ovarian cancer syndrome 2020-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000019251 SCV000154021 likely benign Breast-ovarian cancer, familial 1 2014-02-18 criteria provided, single submitter literature only
GeneDx RCV000120283 SCV000167280 benign not specified 2013-11-04 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 RCV000162566 SCV000212979 benign Hereditary cancer-predisposing syndrome 2014-07-14 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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 RCV000019251 SCV000267702 benign Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000047867 SCV000297225 likely benign Hereditary breast and ovarian cancer syndrome 2015-11-06 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120283 SCV000311791 benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120283 SCV000336440 benign not specified 2015-10-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000047867 SCV000494310 benign Hereditary breast and ovarian cancer syndrome 2014-10-06 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120283 SCV000538437 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: 0.2% (145/66714) European chromosomes; ClinVar: 7 labs classify as benign
Baylor Genetics RCV000457953 SCV000540974 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120283 SCV000586885 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034733 SCV000600292 benign not provided 2019-02-25 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162566 SCV000683041 likely benign Hereditary cancer-predisposing syndrome 2014-12-13 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000019251 SCV000743415 benign Breast-ovarian cancer, familial 1 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000019251 SCV000744655 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Mendelics RCV000019251 SCV001140573 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283015 SCV001156725 benign none provided 2020-08-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000019251 SCV001280881 likely benign Breast-ovarian cancer, familial 1 2019-01-30 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170820 SCV001333438 benign Breast and/or ovarian cancer 2019-03-14 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000457953 SCV001369371 likely benign Familial cancer of breast 2019-11-08 criteria provided, single submitter clinical testing This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BP1,BP4,BP6.
Research and Development, ARUP Laboratories RCV001659717 SCV001878250 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
OMIM RCV000019251 SCV000039539 uncertain significance Breast-ovarian cancer, familial 1 2012-11-01 no assertion criteria provided literature only
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034733 SCV000043175 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
Sharing Clinical Reports Project (SCRP) RCV000019251 SCV000053650 benign Breast-ovarian cancer, familial 1 2011-03-01 no assertion criteria provided clinical testing
ITMI RCV000120283 SCV000084435 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000019251 SCV000144466 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Department of Medical Genetics, University Hospital of North Norway RCV000019251 SCV000301432 likely benign Breast-ovarian cancer, familial 1 2016-05-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120283 SCV000591392 benign not specified no assertion criteria provided clinical testing The p.Arg841Trp variant has been previously reported in 16/8958 proband chromosomes (frequency: 0.002) in individuals with breast or ovarian cancer, however, no controls were included in these studies (Barker 1996, Borg 2010, Diez 2003, Janezic 1999, Pal 2004, Shattuck-Eidens 1997). The variant was also listed in the dbSNP database as having an average heterozygosity of 0.006+/-0.056 (ID#:rs1800709), increasing the likelihood this variant does not have clinical significance. The p.Arg841 residue is not conserved in mammals or lower organisms; however, computational analyses (SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. There are also numerous studies in the literature which have attempted to classify this variant using different modeling appoaches but the effect of this variant on protein function remains undetermined (Burk Herrick 2006, Chenevix-Trench 2006, Goldgar 2004, Fleming 2003, Lindor 2011, Petersen 1998). Notably, this variant was reported in the UMD database, 54 times and in 6 individuals with a second pathogenic variant in either the BRCA1 or BRCA2 genes, increasing the likelihood the p.Arg841Trp variant is benign. It is also reported 114 times in the BIC database with unknown clinical consequence, although this high frequency might suggest it is a common benign polymorphism. Finally, this variant was reported by Myriad as a common polymorphism. In summary, based on the above information, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000019251 SCV000733641 benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034733 SCV000778755 benign not provided 2017-03-08 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162566 SCV000787898 likely benign Hereditary cancer-predisposing syndrome 2017-10-10 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000120283 SCV001800207 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120283 SCV001905820 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120283 SCV001951674 benign not specified no assertion criteria provided clinical testing

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