ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1661G>A (p.Arg554Lys)

dbSNP: rs2067134618
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001234174 SCV001406806 uncertain significance Neurofibromatosis, type 2 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 554 of the NF2 protein (p.Arg554Lys). This variant is not present in population databases (gnomAD no frequency). 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: 960618). 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 RCV002402733 SCV002706537 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-01 criteria provided, single submitter clinical testing The p.R554K variant (also known as c.1661G>A), located in coding exon 15 of the NF2 gene, results from a G to A substitution at nucleotide position 1661. The arginine at codon 554 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly 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.

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