ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.3296C>T (p.Pro1099Leu) (rs80357201)

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Total submissions: 14
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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) RCV000112051 SCV000244337 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 = 0.0000000000309
Invitae RCV000195316 SCV000076141 benign Hereditary breast and ovarian cancer syndrome 2018-01-12 criteria provided, single submitter clinical testing
GeneDx RCV000048128 SCV000167290 benign not specified 2014-01-23 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000112051 SCV000195917 benign Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162544 SCV000212948 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Vantari Genetics RCV000162544 SCV000267007 likely benign Hereditary cancer-predisposing syndrome 2016-01-21 criteria provided, single submitter clinical testing
Counsyl RCV000112051 SCV000488317 benign Breast-ovarian cancer, familial 1 2016-02-25 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000048128 SCV000538448 uncertain significance not specified 2016-06-16 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Multiple papers descrive as non-pathogenic; ClinVar: 4 B/LB
Color RCV000162544 SCV000683096 likely benign Hereditary cancer-predisposing syndrome 2015-02-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034740 SCV000699016 benign not provided 2016-03-25 criteria provided, single submitter clinical testing Variant summary: The variant c.3296C>T affects a conserved nucleotide, leading to amino acid change from Pro to Leu. 3/4 in-silico tools predict this variant to be damaging, however they are not definite. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.0.00026 (32/122380 chromosomes), which does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA1 (0.001). However, the frequency data should still suggest that this variant is likely to be a rare polymorphism. In reputable databases (BIC and UMD), the variant has been reported to co-occur with multiple deleterious pathogenic variants in BRCA1 (p.Glu1060Ter, c.2376_2376delG and c.798_799delTT) as well as in BRCA2 (c.4277delC and c.5353delA). In addition, the variant is also known to be present with a deleterious BRCA1 variant p.Glu1060Ter (Judkins_2005), a definite evidence for benign outcome. Multifactorial probability model studies also show the variant to have a very low probability of being deleterious. Multiple clinical laboratories, reputable databases, and literature classify this variant as benign/polymorphism. Taken all together, this variant has been classified as Benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000112051 SCV000743406 benign Breast-ovarian cancer, familial 1 2014-10-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112051 SCV000744638 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034740 SCV000043168 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112051 SCV000144704 benign Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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