ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1450A>G (p.Met484Val)

gnomAD frequency: 0.00001  dbSNP: rs1182896077
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632644 SCV000753829 uncertain significance Neurofibromatosis, type 2 2022-05-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 527699). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 484 of the NF2 protein (p.Met484Val). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001011649 SCV001171995 benign Hereditary cancer-predisposing syndrome 2022-03-21 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab RCV000632644 SCV002044892 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000632644 SCV004827867 uncertain significance Neurofibromatosis, type 2 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 484 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 NF2-related disorders in the literature. This variant has been identified in 2/251496 chromosomes 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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