ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1391C>T (p.Ala464Val)

gnomAD frequency: 0.00002  dbSNP: rs776109136
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553100 SCV000628852 uncertain significance Neurofibromatosis, type 2 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 464 of the NF2 protein (p.Ala464Val). 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: 457898). 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.
GeneDx RCV002286750 SCV002577163 uncertain significance not provided 2022-04-01 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: 17134719, 16324214, 22482125, 29975249)
Ambry Genetics RCV002395308 SCV002696139 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-17 criteria provided, single submitter clinical testing The p.A464V variant (also known as c.1391C>T), located in coding exon 13 of the NF2 gene, results from a C to T substitution at nucleotide position 1391. The alanine at codon 464 is replaced by valine, an amino acid with similar properties. This amino acid position is not 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.

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