ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1300G>A (p.Glu434Lys)

gnomAD frequency: 0.00003  dbSNP: rs992662337
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632645 SCV000753830 uncertain significance Neurofibromatosis, type 2 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 434 of the NF2 protein (p.Glu434Lys). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 527700). 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 RCV002385991 SCV002691166 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-20 criteria provided, single submitter clinical testing The p.E434K variant (also known as c.1300G>A), located in coding exon 12 of the NF2 gene, results from a G to A substitution at nucleotide position 1300. The glutamic acid at codon 434 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly 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.

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