ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1534C>T (p.Leu512Phe) (rs41286294)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131272 SCV000186240 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000031001 SCV000144128 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761121 SCV000891037 uncertain significance B lymphoblastic leukemia lymphoma with hyperdiploidy 2016-10-06 no assertion criteria provided clinical testing
Color RCV000131272 SCV000902901 likely benign Hereditary cancer-predisposing syndrome 2016-01-14 criteria provided, single submitter clinical testing
Counsyl RCV000031001 SCV000488220 uncertain significance Breast-ovarian cancer, familial 1 2016-09-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724518 SCV000224997 uncertain significance not provided 2015-01-07 criteria provided, single submitter clinical testing
GeneDx RCV000047517 SCV000209929 likely benign not specified 2017-04-18 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.
Integrated Genetics/Laboratory Corporation of America RCV000047517 SCV000698872 likely benign not specified 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1534C>T (p.Leu512Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 276990 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (4e-05 vs 0.001), allowing no conclusion about variant significance. c.1534C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Judkins 2005, Meindl 2002, Pennington 2013, Jimenez 2009, Plaskocinska 2016). These data do not allow any conclusion about variant significance. Several co-occurrences with other pathogenic variants have been reported (in UMD: BRCA1 c.81_4986del (p.Cys27X), BRCA2 c.8023A>G (p.Ile2675Val), BRCA2 c.5909C>A (p.Ser1970X); Jimenez 2009: BRCA1 c.1570delG (p.Ala524Glnfs); and in an internal sample: BRCA2 c.1813dupA (p.Ile605fsX11)), 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 classified the variant as Likely Benign (2x) or VUS (4x). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000167769 SCV000075530 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031001 SCV000296346 uncertain significance Breast-ovarian cancer, familial 1 2016-03-25 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031001 SCV000053593 likely benign Breast-ovarian cancer, familial 1 2012-07-05 no assertion criteria provided clinical testing

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