ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1459A>C (p.Ile487Leu) (rs147506929)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011680 SCV001172030 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-25 criteria provided, single submitter clinical testing The p.I487L variant (also known as c.1459A>C), located in coding exon 14 of the NF2 gene, results from an A to C substitution at nucleotide position 1459. The isoleucine at codon 487 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001045754 SCV001209625 uncertain significance Neurofibromatosis, type 2 2019-04-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 487 of the NF2 protein (p.Ile487Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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