ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4535G>T (p.Ser1512Ile) (rs1800744)

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Total submissions: 27
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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) RCV000112356 SCV000244362 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 = 0.00000000000309
Invitae RCV000048591 SCV000076604 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000112356 SCV000154028 benign Breast-ovarian cancer, familial 1 2014-03-19 criteria provided, single submitter literature only
Michigan Medical Genetics Laboratories,University of Michigan RCV000112356 SCV000195930 benign Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162492 SCV000212874 benign Hereditary cancer-predisposing syndrome 2014-07-21 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120258 SCV000226128 benign not specified 2014-07-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000048591 SCV000494296 benign Hereditary breast and ovarian cancer syndrome 2014-01-24 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120258 SCV000586900 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120258 SCV000593659 benign not specified 2016-12-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283304 SCV000602672 benign none provided 2020-06-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162492 SCV000683192 likely benign Hereditary cancer-predisposing syndrome 2014-11-11 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000112356 SCV000743392 benign Breast-ovarian cancer, familial 1 2014-10-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112356 SCV000744613 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120258 SCV000806953 benign not specified 2016-11-07 criteria provided, single submitter clinical testing
Mendelics RCV000112356 SCV001140518 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000112356 SCV001280758 benign Breast-ovarian cancer, familial 1 2018-08-07 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120258 SCV001469392 benign not specified 2020-06-15 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034752 SCV000043157 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000120258 SCV000084410 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000112356 SCV000145117 benign Breast-ovarian cancer, familial 1 1999-06-21 no assertion criteria provided clinical testing
Pathway Genomics RCV000112356 SCV000187728 likely benign Breast-ovarian cancer, familial 1 2014-07-24 no assertion criteria provided literature only
Sharing Clinical Reports Project (SCRP) RCV000112356 SCV000189343 benign Breast-ovarian cancer, familial 1 2011-03-08 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000120258 SCV000587407 benign not specified 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120258 SCV000591526 benign not specified no assertion criteria provided clinical testing The BRCA1, c.4535G>T, p.Ser1512Ile variant has been reported in the literature in 6/2156 proband chromosomes of individuals with HBOC and sporadic breast/ ovarian cancer. It was also identified in 6/1360 of the control chromosomes evaluated (Al-Mulla_2008, Bergthorsson_2001, Young_2009, Wagner_1998, Tavtigian_2006, Phelan_2005, Sanz_2010). The variant has also been previously identified in our laboratory in 6 individuals, and was classified as benign. The variant is reported in the BIC (x58), Exome Server and BOCs databases. It is also listed in the dbSNP database as coming from a "clinical source" (ID#: rs1800744) with a MAF score of 0.001 (1000 Genomes), increasing the likelihood that this is a low frequency benign variant. The residue is not conserved in mammals, and computational analyses (PolyPhen, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein. However, this information is not very predictive of pathogenicity. Functional studies examining the effect of the variant on transcriptional activation found that the variant levels were equal to or higher than that of wild type BRCA1, suggesting that it does not represent a high risk variant & is likely to have low clinical significance (Phelan_2005). Studies have also reported that p.Ser1512Ile has been found to co-occur with other known BRCA1 pathogenic variants numerous times, increasing the likelihood that this variant does not have clinical significance (Bergthorsson_2001, Tavtigian_2006, Phelan_2005). In summary, based on the above information, this variant is classified as Benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000112356 SCV000733609 benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034752 SCV000778738 benign not provided 2016-12-06 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162492 SCV000805231 likely benign Hereditary cancer-predisposing syndrome 2018-04-25 no assertion criteria provided clinical testing

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