ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3952A>G (p.Ile1318Val) (rs397509121)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480977 SCV000568410 uncertain significance not provided 2018-06-07 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3952A>G at the cDNA level, p.Ile1318Val (I1318V) at the protein level, and results in the change of an Isoleucine to a Valine (ATT>GTT). Using alternate nomenclature, this variant has been previously published as BRCA1 4071A>G. This variant has been identified in at least two breast/ovarian cancer families (Arnold 1999, Meindl 2002). BRCA1 Ile1318Val 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. BRCA1 Ile1318Val occurs at a position that is not conserved and is located in the SCD domain and a region known to interact with multiple other proteins (Chen 1998, Narod 2004, Clark 2012). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Ile1318Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000509595 SCV000607980 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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