ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1384C>T (p.Arg462Cys)

dbSNP: rs771143279
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001339097 SCV001532818 uncertain significance Neurofibromatosis, type 2 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 462 of the NF2 protein (p.Arg462Cys). 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 variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1036137). 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 with a positive 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 RCV002395739 SCV002699016 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-23 criteria provided, single submitter clinical testing The p.R462C variant (also known as c.1384C>T), located in coding exon 13 of the NF2 gene, results from a C to T substitution at nucleotide position 1384. The arginine at codon 462 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well 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.
Revvity Omics, Revvity RCV001339097 SCV003815872 uncertain significance Neurofibromatosis, type 2 2020-03-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001339097 SCV004825640 uncertain significance Neurofibromatosis, type 2 2023-11-30 criteria provided, single submitter clinical testing

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