Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069189 | SCV001234341 | uncertain significance | Neurofibromatosis, type 1 | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 525 of the NF1 protein (p.Leu525Ile). This variant is not present in population databases (gnomAD no frequency). 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: 862461). 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 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 | RCV002402469 | SCV002704093 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-06-28 | criteria provided, single submitter | clinical testing | The p.L525I variant (also known as c.1573T>A), located in coding exon 14 of the NF1 gene, results from a T to A substitution at nucleotide position 1573. The leucine at codon 525 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly 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. |