ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1445C>G (p.Pro482Arg) (rs766339217)

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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 RCV000571543 SCV000674158 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-05 criteria provided, single submitter clinical testing The p.P482R variant (also known as c.1445C>G), located in coding exon 13 of the NF2 gene, results from a C to G substitution at nucleotide position 1445. The proline at codon 482 is replaced by arginine, an amino acid with dissimilar 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 RCV001048459 SCV001212466 uncertain significance Neurofibromatosis, type 2 2020-09-11 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 482 of the NF2 protein (p.Pro482Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. 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. ClinVar contains an entry for this variant (Variation ID: 485992). 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.

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