ClinVar Miner

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

dbSNP: rs147506929
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Total submissions: 4
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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 2023-10-23 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 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 487 of the NF2 protein (p.Ile487Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 819269). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF2 protein function with a negative predictive value of 80%. 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.
Genome-Nilou Lab RCV001045754 SCV002044894 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001045754 SCV004843111 uncertain significance Neurofibromatosis, type 2 2023-11-30 criteria provided, single submitter clinical testing

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