ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1557G>A (p.Met519Ile)

dbSNP: rs1601659358
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820145 SCV000960843 uncertain significance Neurofibromatosis, type 2 2018-08-26 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with NF2-related disease. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 519 of the NF2 protein (p.Met519Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine.
GeneDx RCV001759604 SCV001987304 uncertain significance not provided 2020-12-17 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV000820145 SCV002044902 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing

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