ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1397G>A (p.Arg466Gln)

dbSNP: rs866689896
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531371 SCV000628853 uncertain significance Neurofibromatosis, type 2 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 466 of the NF2 protein (p.Arg466Gln). This variant is not present in population databases (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: 457899). 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 RCV001011356 SCV001171665 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-05 criteria provided, single submitter clinical testing The p.R466Q variant (also known as c.1397G>A), located in coding exon 13 of the NF2 gene, results from a G to A substitution at nucleotide position 1397. The arginine at codon 466 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.
Genome-Nilou Lab RCV000531371 SCV002044887 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003326452 SCV004033937 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing NF2: PM2, BP1

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