ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1688A>G (p.Asn563Ser)

gnomAD frequency: 0.00001  dbSNP: rs768303416
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000792025 SCV000931297 uncertain significance Neurofibromatosis, type 2 2023-08-16 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 639272). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 563 of the NF2 protein (p.Asn563Ser).
Ambry Genetics RCV001012713 SCV001173201 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-19 criteria provided, single submitter clinical testing The p.N563S variant (also known as c.1688A>G), located in coding exon 15 of the NF2 gene, results from an A to G substitution at nucleotide position 1688. The asparagine at codon 563 is replaced by serine, 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.
Genome-Nilou Lab RCV000792025 SCV002044908 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000792025 SCV004821919 uncertain significance Neurofibromatosis, type 2 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 563 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 hereditary cancer 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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