ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.652G>T (p.Gly218Cys)

dbSNP: rs776818377
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001313568 SCV001504068 uncertain significance Neurofibromatosis, type 2 2023-06-25 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 expected to disrupt NF2 protein function. ClinVar contains an entry for this variant (Variation ID: 1014785). This variant has not been reported in the literature in individuals affected with NF2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 218 of the NF2 protein (p.Gly218Cys).
Ambry Genetics RCV002366162 SCV002657935 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-03 criteria provided, single submitter clinical testing The p.G218C variant (also known as c.652G>T), located in coding exon 7 of the NF2 gene, results from a G to T substitution at nucleotide position 652. The glycine at codon 218 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003317476 SCV004021796 uncertain significance not provided 2023-01-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11756419, 16324214, Javaid2021[Computational])

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