ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3055A>G (p.Ile1019Val) (rs80357311)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132486 SCV000187580 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031085 SCV000144626 uncertain significance Breast-ovarian cancer, familial 1 2001-10-29 no assertion criteria provided clinical testing
Color RCV000132486 SCV000688418 likely benign Hereditary cancer-predisposing syndrome 2015-06-01 criteria provided, single submitter clinical testing
Counsyl RCV000031085 SCV000487925 uncertain significance Breast-ovarian cancer, familial 1 2015-12-10 criteria provided, single submitter clinical testing
GeneDx RCV000420120 SCV000516821 likely benign not specified 2017-07-10 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 RCV000589797 SCV000699000 uncertain significance not provided 2016-12-27 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3055A>G (p.Ile1019Val) variant located in the DNA binding domain (via Lu_2015) causes a missense change, which 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome. A functional study, Lu_2015 found that the variant of interest acted comparably to the wild type for HDR activity. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/121332, which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. Multiple publications have cited the variant in an affected individual, although limited information was provided (ie, lack of cosegregation and/or co-occurrence). Multiple clinical diagnostic laboratories have cited the variant as "likely benign." Therefore, the variant of interest has been classified as a "Variant of Uncertain Significance - Possibly Benign," until additional information becomes available.
Invitae RCV000048061 SCV000076074 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1019 of the BRCA1 protein (p.Ile1019Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs80357311, ExAC 0.001%). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 37504). Experimental studies investigating homology-directed repair (HDR) have shown that this missense change functions similar to wild type protein (PMID: 26689913). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031085 SCV000053681 likely benign Breast-ovarian cancer, familial 1 2010-02-01 no assertion criteria provided clinical testing

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