ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1469C>T (p.Pro490Leu) (rs765100922)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688163 SCV000815765 uncertain significance Neurofibromatosis, type 2 2020-09-23 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 490 of the NF2 protein (p.Pro490Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs765100922, ExAC 0.003%). This variant has not been reported in the literature in individuals with NF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Ambry Genetics RCV001011729 SCV001172086 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-21 criteria provided, single submitter clinical testing The p.P490L variant (also known as c.1469C>T), located in coding exon 14 of the NF2 gene, results from a C to T substitution at nucleotide position 1469. The proline at codon 490 is replaced by leucine, an amino acid with 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.

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