ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5137G>A (p.Val1713Ile) (rs1064793309)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484213 SCV000565729 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5137G>A at the cDNA level, p.Val1713Ile (V1713I) at the protein level, and results in the change of a Valine to an Isoleucine (GTA>ATA). Using alternate nomenclature, this variant would be defined as BRCA1 5256G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Val1713Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Val1713Ile occurs at a position where amino acids with properties similar to Valine are tolerated across species and is located within the BRCT1 domain and a region of interaction with multiple proteins (Paul 2014, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Val1713Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV001228454 SCV001400854 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-08-13 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1713 of the BRCA1 protein (p.Val1713Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 418578). This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). This variant disrupts the p.Val1713 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7611277, 25556971, 17305420, 20516115, 30209399, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV001077648 SCV001243606 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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