ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3691T>C (p.Phe1231Leu) (rs41293451)

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Total submissions: 9
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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 2018-01-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131521 SCV000186515 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
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 RCV000031122 SCV000296415 uncertain significance Breast-ovarian cancer, familial 1 2016-06-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048282 SCV000699058 uncertain significance not specified 2019-01-08 criteria provided, single submitter clinical testing Variant summary: The variant, 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 damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 277002 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.3691T>C has been reported in the literature in individuals affected with breast cancer (Pal_2015, Zabala_2018). These reports, however do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (PMS2 c.2186_2187delTC, p.Leu729fsX6), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2x likely benign, 2x VUS). Based on the evidence outlined above, the variant was classified as uncertain significance.
Mendelics RCV000195391 SCV000839250 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000131521 SCV000902939 benign Hereditary cancer-predisposing syndrome 2016-02-24 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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