ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3349A>G (p.Ile1117Val) (rs397507307)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480421 SCV000571742 uncertain significance not provided 2016-09-20 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3349A>G at the cDNA level, p.Ile1117Val (I1117V) at the protein level, and results in the change of an Isoleucine to a Valine (ATA>GTA). Using alternate nomenclature, this variant would be defined as BRCA2 3577A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ile1117Val 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 Isoleucine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ile1117Val occurs at a position that is conserved across species and is located in the region of interaction with RAD51 (Roy 2012). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Ile1117Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000688673 SCV000816295 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-30 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1117 of the BRCA2 protein (p.Ile1117Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 37837). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Color RCV000772028 SCV000904996 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-20 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031418 SCV000054023 uncertain significance Breast-ovarian cancer, familial 2 2010-03-16 no assertion criteria provided clinical testing

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