ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.4754T>C (p.Leu1585Pro) (rs56119278)

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Total submissions: 11
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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) RCV000112385 SCV000244368 benign Breast-ovarian cancer, familial 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 = 0.000102
Invitae RCV000167813 SCV000076645 benign Hereditary breast and ovarian cancer syndrome 2017-12-29 criteria provided, single submitter clinical testing
GeneDx RCV000120262 SCV000209974 benign not specified 2017-06-27 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.
Ambry Genetics RCV000162687 SCV000213141 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Color RCV000162687 SCV000683208 likely benign Hereditary cancer-predisposing syndrome 2015-05-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587835 SCV000699165 benign not provided 2016-03-17 criteria provided, single submitter clinical testing Variant summary: Variant affects a non-conserved nucleotide and results in a replacement of a medium size and hydrophobic Leucine (L) with a medium size and hydrophobic Proline (P). 3/4 in silico tools predict the variant to be neutral. It was observed predominantly in the African subcohorts of the ExAC project at an allele frequency of 0.13% which slightly exceeds the maximal expected allele frequency of a disease causing BRCA1 allele (0.1%). It was reported in several HBOC spectrum patients however without strong evidence for pathogenicity. The variant was observed to co-occur with pathogenic/possibly pathogenic BRCA1 and BRCA2 variants such as BRCA1 p.C64Y; p.Lys1290Ter, p.Val738fs, c.824ins10 and BRCA2 p.Lys1872_Ile1874fs indicating neutrality. A benign impact is also supported by computational analysis that integrated multiple forms of genetic evidence for the variant of interest (Lindor_2012). Carvalho_2007 showed decreased transcriptional activity in yeast and mammalian cells; however, Hayes_2000 showed transcription activation of the variant is comparable to wild-type BRCA1 in yeast. In addition, multiple literature and reputable databases/clinical laboratories classify this variant as likely benign or benign. Considering all evidence, the variant was classified as Benign.
PreventionGenetics,PreventionGenetics RCV000587835 SCV000806959 likely benign not provided 2017-07-11 criteria provided, single submitter clinical testing
ITMI RCV000120262 SCV000084414 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000112385 SCV000145161 benign Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148377 SCV000190075 likely benign Neoplasm of the breast 2014-06-01 no assertion criteria provided research
True Health Diagnostics RCV000162687 SCV000787905 likely benign Hereditary cancer-predisposing syndrome 2018-01-03 no assertion criteria provided clinical testing

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