ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.74G>A (p.Arg25Lys)

dbSNP: rs1569259813
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703501 SCV000832404 uncertain significance Neurofibromatosis, type 2 2019-06-30 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with NF2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 25 of the NF2 protein (p.Arg25Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine.
Ambry Genetics RCV001026507 SCV001188902 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-02 criteria provided, single submitter clinical testing The p.R25K variant (also known as c.74G>A), located in coding exon 1 of the NF2 gene, results from a G to A substitution at nucleotide position 74. The arginine at codon 25 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly 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.
Genome-Nilou Lab RCV000703501 SCV002044835 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003465626 SCV004199046 uncertain significance Familial meningioma 2023-08-14 criteria provided, single submitter clinical testing

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