ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1379T>C (p.Ile460Thr)

dbSNP: rs147417054
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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 RCV000803750 SCV000943635 uncertain significance Neurofibromatosis, type 1 2024-11-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 460 of the NF1 protein (p.Ile460Thr). This variant is present in population databases (rs147417054, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 648920). 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 NF1 protein function with a negative predictive value of 95%. 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 RCV002319108 SCV001171554 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-07-07 criteria provided, single submitter clinical testing The p.I460T variant (also known as c.1379T>C), located in coding exon 12 of the NF1 gene, results from a T to C substitution at nucleotide position 1379. The isoleucine at codon 460 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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.
Genome-Nilou Lab RCV000803750 SCV002561905 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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