ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.170G>A (p.Arg57Gln) (rs368773485)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531276 SCV000628859 uncertain significance Neurofibromatosis, type 2 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 57 of the NF2 protein (p.Arg57Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs368773485, ExAC 0.003%) but has not been reported in the literature in individuals with an NF2-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567851 SCV000674140 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-23 criteria provided, single submitter clinical testing The p.R57Q variant (also known as c.170G>A), located in coding exon 2 of the NF2 gene, results from a G to A substitution at nucleotide position 170. The arginine at codon 57 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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