ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3607C>T (p.Arg1203Ter) (rs62625308)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 27
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000019240 SCV000282311 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048251 SCV000076264 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1203*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with breast and ovarian cancer, and has been reported to segregate with disease in a family (PMID: 7894493, 21324516, 22006311, 22752604, 24010542). This sequence change is also known as 3726C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 17671). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131818 SCV000186873 pathogenic Hereditary cancer-predisposing syndrome 2018-09-28 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000159978 SCV000210150 pathogenic not provided 2018-10-02 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.3607C>T at the cDNA level and p.Arg1203Ter (R1203X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as 3726C>T using alternate nomenclature, has been reported in association with breast and ovarian cancer (Friedman 1994, Walsh 2011, Zhang 2011). We therefore consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159978 SCV000296328 pathogenic not provided 2015-04-21 criteria provided, single submitter clinical testing
GeneKor MSA RCV000239343 SCV000296797 pathogenic Familial cancer of breast 2020-01-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1203, p.(Arg1203*). It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in individuals and families affected by breast and ovarian cancer and was shown to segregate with disease in one family (PMID: 21324516, 22006311). This sequence change is also known as 3726C>T in the literature. This mutation has been described in the mutation database ClinVar (Variation ID:17671).
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735444 SCV000324835 pathogenic Breast and/or ovarian cancer 2016-03-13 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000019240 SCV000325699 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000019240 SCV000488004 pathogenic Breast-ovarian cancer, familial 1 2015-12-16 criteria provided, single submitter clinical testing
Color RCV000131818 SCV000537658 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV000239343 SCV000540941 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000019240 SCV000564385 pathogenic Breast-ovarian cancer, familial 1 2016-04-11 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000048251 SCV000588046 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048251 SCV000591455 pathogenic Hereditary breast and ovarian cancer syndrome 2013-06-25 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000048251 SCV000605742 pathogenic Hereditary breast and ovarian cancer syndrome 2019-04-24 criteria provided, single submitter clinical testing The p.Arg1203X variant in BRCA1 has been reported in >40 individuals with BRCA1-associated cancers (Friedman 1994, Manguoglu 2003, Walsh 2011, Solano 2012, Kim 2012, Juwle 2012, Couch 2015, Breast Cancer Information Core (BIC) database, Sharing Clinical Reports Project). This variant has been identified in 1/17194 East Asian and 2/111402 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs62625308). This nonsense variant leads to a premature termination codon at position 1203, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in individuals with hereditary breast and ovarian cancer (HBOC). In addition, this variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000282311.1). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner. ACMG/AMP Criteria applied: PVS1, PM2, PS4.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000019240 SCV000744631 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677815 SCV000803975 pathogenic Ovarian cancer 2017-02-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048251 SCV000918688 pathogenic Hereditary breast and ovarian cancer syndrome 2019-08-13 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3607C>T (p.Arg1203X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251014 control chromosomes. c.3607C>T has been reported in the literature in numerous individuals affected with hereditary or early-onset breast and/or ovarian cancer (ie. Friedman_1994, Meindl_2002, Kim_2012, Juwle_2012, Solano_2013, Stavropoulo_2013). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 16 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (after 2014). All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000239343 SCV001251952 pathogenic Familial cancer of breast 2020-05-03 criteria provided, single submitter clinical testing
OMIM RCV000019240 SCV000039528 pathogenic Breast-ovarian cancer, familial 1 1994-12-01 no assertion criteria provided literature only
Sharing Clinical Reports Project (SCRP) RCV000019240 SCV000053711 pathogenic Breast-ovarian cancer, familial 1 2012-10-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000019240 SCV000144807 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148389 SCV000190087 pathogenic Neoplasm of the breast 2014-06-01 no assertion criteria provided research
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048251 SCV000587321 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000019240 SCV000733624 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735444 SCV000863580 pathogenic Breast and/or ovarian cancer 2013-12-20 no assertion criteria provided clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785373 SCV000923944 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.