ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1660_1661del (p.Arg554fs) (rs1601666191)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804920 SCV000944858 uncertain significance Neurofibromatosis, type 2 2018-08-02 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NF2 gene (p.Arg554Glyfs*10). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated NF2 protein. 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 disease. This variant disrupts the C-terminal domain of the NF2 protein, which contains a sub-domain composed of 47 amino acid residues (amino acids 532-579) thought to be involved in cell proliferation regulation. An experimental study has shown that deletion of these 47 amino acid residues abrogates the ability of the NF2 protein to inhibit cell proliferation in NF2-deficient cultured cells (PMID: 19910496). However, experimental studies and prediction algorithms are not available for this specific variant, and the functional significance of the disrupted amino acids is currently unknown. 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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