ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.831T>G (p.Asp277Glu) (rs762883753)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001017547 SCV001178638 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-05 criteria provided, single submitter clinical testing The p.D277E variant (also known as c.831T>G), located in coding exon 9 of the NF2 gene, results from a T to G substitution at nucleotide position 831. The aspartic acid at codon 277 is replaced by glutamic acid, 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.
Invitae RCV001206141 SCV001377436 uncertain significance Neurofibromatosis, type 2 2019-06-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 277 of the NF2 protein (p.Asp277Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs762883753, ExAC 0.002%). This variant has not been reported in the literature in individuals with NF2-related conditions. 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.

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