ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4261C>T (p.His1421Tyr) (rs80357013)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084565 SCV000076519 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131530 SCV000186524 likely benign Hereditary cancer-predisposing syndrome 2019-12-16 criteria provided, single submitter clinical testing Insufficient evidence
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000679697 SCV000225646 uncertain significance not provided 2015-03-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679697 SCV000296414 uncertain significance not provided 2019-10-25 criteria provided, single submitter clinical testing
Counsyl RCV000112306 SCV000489251 uncertain significance Breast-ovarian cancer, familial 1 2016-09-09 criteria provided, single submitter clinical testing
GeneDx RCV000174360 SCV000729079 likely benign not specified 2017-10-30 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.
PreventionGenetics,PreventionGenetics RCV000679697 SCV000806948 uncertain significance not provided 2018-01-04 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131530 SCV000903403 likely benign Hereditary cancer-predisposing syndrome 2017-06-20 criteria provided, single submitter clinical testing
Mendelics RCV000112306 SCV001140530 uncertain significance Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000174360 SCV001361787 likely benign not specified 2020-11-19 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4261C>T (p.His1421Tyr) 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 1.2e-05 in 252434 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4261C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer or at high risk, without strong evidence for causality (e.g. Shattuck-Eidens_1997, Dutil_2012, Vogel_2007, Judkins_2005, Diaz-Zabala_2018, Grant_2015). However, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrence with another pathogenic variant has been reported (Dutil_2012, pathogenic variant not provided) for this variant, supporting evidence for a benign role. Several functional experiments suggest that this variant has transcriptional and HDR activity similar to that of wild-type (Carvalho_2010, Hu_2002, Lu_2015, Woods_2016). Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign n=3, VUS n=6). Based on the evidence outlined above, the variant was classified as likely benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112306 SCV000145044 uncertain significance Breast-ovarian cancer, familial 1 1997-02-15 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112306 SCV000297610 likely benign Breast-ovarian cancer, familial 1 2010-02-03 no assertion criteria provided clinical testing

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