ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.683A>G (p.Lys228Arg)

gnomAD frequency: 0.00002  dbSNP: rs145384260
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632636 SCV000753821 uncertain significance Neurofibromatosis, type 2 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 228 of the NF2 protein (p.Lys228Arg). This variant is present in population databases (rs145384260, gnomAD 0.0009%). 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: 527691). 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 RCV001025713 SCV001187957 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-12 criteria provided, single submitter clinical testing The p.K228R variant (also known as c.683A>G), located in coding exon 8 of the NF2 gene, results from an A to G substitution at nucleotide position 683. The lysine at codon 228 is replaced by arginine, 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 RCV000632636 SCV002044857 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003459508 SCV004199032 uncertain significance Familial meningioma 2023-10-27 criteria provided, single submitter clinical testing

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