Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002340222 | SCV002636132 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-02-22 | criteria provided, single submitter | clinical testing | The p.L1522P variant (also known as c.4565T>C), located in coding exon 34 of the NF1 gene, results from a T to C substitution at nucleotide position 4565. The leucine at codon 1522 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003598083 | SCV004406359 | uncertain significance | Neurofibromatosis, type 1 | 2022-10-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NF1-related conditions. 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 expected to disrupt NF1 protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1522 of the NF1 protein (p.Leu1522Pro). |