ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.658A>T (p.Asn220Tyr) (rs1601618646)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796728 SCV000936253 pathogenic Neurofibromatosis, type 2 2019-02-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with tyrosine at codon 220 of the NF2 protein (p.Asn220Tyr). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with neurofibromatosis type 2 in a family (PMID: 8230593). This variant has been reported to affect NF2 protein function (PMID: 10712203). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001578021 SCV001805537 pathogenic not provided 2020-01-08 criteria provided, single submitter clinical testing Exonic splice site variant demonstrated to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Protein based functional studies are conflicting with respect to protein and cytoskeletal binding, dimerization, and cellular localization (Deguen 1988, Murthy 1998, Stokowski 2000, Scoles 2002); however, as the mechanism of pathogenicity of this variant is aberrant splicing, these studies are not relevant; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 3134615, 8230593, 8755919, 11756419, 9425229, 9430655, 11779178, 10712203, 8012353)

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