ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.842A>T (p.Asp281Val)

dbSNP: rs2147033520
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001913960 SCV002187826 uncertain significance Neurofibromatosis, type 2 2023-06-14 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 1420017). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 281 of the NF2 protein (p.Asp281Val).
Ambry Genetics RCV003375445 SCV004098381 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-29 criteria provided, single submitter clinical testing The p.D281V variant (also known as c.842A>T), located in coding exon 9 of the NF2 gene, results from an A to T substitution at nucleotide position 842. The aspartic acid at codon 281 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health RCV001913960 SCV004828107 uncertain significance Neurofibromatosis, type 2 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with valine at codon 281 of the NF2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with NF2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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