ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5155G>T (p.Val1719Leu) (rs749465132)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236215 SCV000293254 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5155G>T at the cDNA level, p.Val1719Leu (V1719L) at the protein level, and results in the change of a Valine to a Leucine (GTG>TTG). Using alternate nomenclature, this variant would be defined as BRCA1 5274G>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Val1719Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the BRCT1 domain and a region known to interact with multiple other proteins (Narod 2004, Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Val1719Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001023635 SCV001185544 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-04 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001041311 SCV001204917 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-03-07 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 1719 of the BRCA1 protein (p.Val1719Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs749465132, ExAC 0.009%). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 245993). This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). 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.
Brotman Baty Institute,University of Washington RCV001076110 SCV001241801 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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