Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003495498 | SCV004248877 | uncertain significance | Neurofibromatosis, type 1 | 2023-03-29 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 795 of the NF1 protein (p.Pro795Leu). 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. 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. |
| Ambry Genetics | RCV004992624 | SCV005454549 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-10-15 | criteria provided, single submitter | clinical testing | The p.P795L variant (also known as c.2384C>T), located in coding exon 20 of the NF1 gene, results from a C to T substitution at nucleotide position 2384. The proline at codon 795 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |