ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1058G>A (p.Arg353Lys)

dbSNP: rs2147072682
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001946145 SCV002211280 uncertain significance Neurofibromatosis, type 2 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 353 of the NF2 protein (p.Arg353Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002407114 SCV002715202 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-06 criteria provided, single submitter clinical testing The p.R353K variant (also known as c.1058G>A), located in coding exon 11 of the NF2 gene, results from a G to A substitution at nucleotide position 1058. The arginine at codon 353 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is 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.
All of Us Research Program, National Institutes of Health RCV001946145 SCV004837096 uncertain significance Neurofibromatosis, type 2 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 353 of the NF2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with NF2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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