ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3691T>C (p.Phe1231Leu) (rs41293451)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195391 SCV000076295 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131521 SCV000186515 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.
GeneDx RCV000048282 SCV000209955 likely benign not specified 2017-12-27 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281713 SCV000296415 likely benign not provided 2019-12-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000048282 SCV000699058 uncertain significance not specified 2020-10-02 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3691T>C (p.Phe1231Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251286 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3691T>C has been reported in the literature in individuals affected with Breast And Ovarian Cancer Syndrome (Pal_2015, Zabala_2018). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrence with a pathogenic variant has been reported (BRCA2 c.518delG, p.Gly173ValfsX12), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and reported the variant with conflicting assessments (benign/likely benign n=3, VUS n=3). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Mendelics RCV000195391 SCV000839250 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131521 SCV000902939 benign Hereditary cancer-predisposing syndrome 2016-02-24 criteria provided, single submitter clinical testing
Mendelics RCV000031122 SCV001140548 uncertain significance Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031122 SCV000053720 benign Breast-ovarian cancer, familial 1 2010-02-25 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031122 SCV000144836 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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