ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.497A>T (p.Glu166Val)

dbSNP: rs779353677
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687173 SCV000814726 uncertain significance Neurofibromatosis, type 2 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 166 of the NF2 protein (p.Glu166Val). This variant is present in population databases (rs779353677, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 567169). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF2 protein function with a negative predictive value of 80%. 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 RCV002334259 SCV002643486 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-17 criteria provided, single submitter clinical testing The p.E166V variant (also known as c.497A>T), located in coding exon 5 of the NF2 gene, results from an A to T substitution at nucleotide position 497. The glutamic acid at codon 166 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is well 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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