ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3608G>A (p.Arg1203Gln)

gnomAD frequency: 0.00006  dbSNP: rs55930959
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Total submissions: 16
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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) RCV000112134 SCV000244343 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 = 0.00000365
Invitae RCV000048252 SCV000076265 likely benign Hereditary breast ovarian cancer syndrome 2024-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162979 SCV000213467 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: 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.
Pathway Genomics RCV000112134 SCV000223747 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2014-10-30 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000048252 SCV000258060 uncertain significance Hereditary breast ovarian cancer syndrome 2015-07-15 criteria provided, single submitter clinical testing
Counsyl RCV000112134 SCV000489044 benign Breast-ovarian cancer, familial, susceptibility to, 1 2016-08-10 criteria provided, single submitter clinical testing
GeneDx RCV000588566 SCV000515531 likely benign not provided 2020-10-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21990134, 20104584, 21218378, 18284688, 19471317, 21520273, 21120943, 15447980, 15235020, 25011685, 22753008, 17924331, 27376475, 25948282, 18273839, 15983021, 23704879, 16267036, 15385441, 33087888)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000428879 SCV000699045 benign not specified 2021-07-04 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3608G>A (p.Arg1203Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 251078 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (4.8e-05 vs 0.001), allowing no conclusion about variant significance. c.3608G>A has been widely reported in the literature in individuals undergoing sequence based analysis for Hereditary Breast And Ovarian Cancer Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Multifactorial probability models have classified this variant as neutral/benign with an IARC classification of 1 (benign) (example, Easton_2007, Lindor_2012, Lyra_2021). At-least two co-occurrences with other pathogenic variant(s) have been reported in the BIC database and observed at our laboratory (BIC, BRCA2 c.778_779delGA, p.Glu260Serfs; Our lab, BRIP1 c.890delA, p.Lys297fs), providing supporting evidence for a benign role. Multiple clinical diagnostic laboratories and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a majority consensus leaning towards benign/likely benign (n=6). Based on the evidence outlined above, the variant was classified as benign.
Color Diagnostics, LLC DBA Color Health RCV000162979 SCV000903322 likely benign Hereditary cancer-predisposing syndrome 2018-05-30 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000588566 SCV001151330 likely benign not provided 2022-09-01 criteria provided, single submitter clinical testing BRCA1: BP1, BP4, BS2
Illumina Laboratory Services, Illumina RCV000112134 SCV001284948 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000428879 SCV004026775 benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588566 SCV004219362 benign not provided 2023-07-21 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112134 SCV000144808 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2002-05-29 no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000588566 SCV001952096 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000428879 SCV001970811 benign not specified no assertion criteria provided clinical testing

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