ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1243A>G (p.Thr415Ala)

dbSNP: rs776970251
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001362142 SCV001558145 uncertain significance Neurofibromatosis, type 2 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 415 of the NF2 protein (p.Thr415Ala). 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: 1053758). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV002384512 SCV002671277 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-14 criteria provided, single submitter clinical testing The p.T415A variant (also known as c.1243A>G), located in coding exon 12 of the NF2 gene, results from an A to G substitution at nucleotide position 1243. The threonine at codon 415 is replaced by alanine, an amino acid with similar properties. This alteration was reported as a germline alteration in an individual who underwent clinical NF2 testing; however phenotypic information for this individual was not available (Ahronowitz I et al. Hum Mutat, 2007 Jan;28:1-12). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002493849 SCV002801475 uncertain significance Familial meningioma; Neurofibromatosis, type 2; SMARCB1-related schwannomatosis 2022-03-22 criteria provided, single submitter clinical testing

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