ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1741A>C (p.Thr581Pro)

dbSNP: rs1601688849
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001012916 SCV001173436 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-12 criteria provided, single submitter clinical testing The p.T581P variant (also known as c.1741A>C), located in coding exon 16 of the NF2 gene, results from an A to C substitution at nucleotide position 1741. The threonine at codon 581 is replaced by proline, an amino acid with highly 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.
All of Us Research Program, National Institutes of Health RCV004004522 SCV004825123 uncertain significance Neurofibromatosis, type 2 2023-08-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV004004522 SCV005772695 uncertain significance Neurofibromatosis, type 2 2024-02-20 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 581 of the NF2 protein (p.Thr581Pro). 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: 819951). 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.

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