Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001223947 | SCV001396118 | uncertain significance | Neurofibromatosis, type 1 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 1287 of the NF1 protein (p.Phe1287Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV002356951 | SCV002622835 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-05-25 | criteria provided, single submitter | clinical testing | The p.F1287L variant (also known as c.3859T>C), located in coding exon 28 of the NF1 gene, results from a T to C substitution at nucleotide position 3859. The phenylalanine at codon 1287 is replaced by leucine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with breast cancer (Weitzel JN et al. Cancer, 2019 08;125:2829-2836). 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. |