Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002382258 | SCV001188010 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-06-28 | criteria provided, single submitter | clinical testing | The p.F2295L variant (also known as c.6885T>G), located in coding exon 46 of the NF1 gene, results from a T to G substitution at nucleotide position 6885. The phenylalanine at codon 2295 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Invitae | RCV002552403 | SCV003197040 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2295 of the NF1 protein (p.Phe2295Leu). 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: 826680). 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 with a positive 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. |
| Baylor Genetics | RCV003461411 | SCV004190719 | uncertain significance | Juvenile myelomonocytic leukemia | 2023-05-23 | criteria provided, single submitter | clinical testing |